<?xml version="1.0" encoding="utf-8"?>
<!--XBRL document created with Toppan Merrill Bridge  10.4.0.13 -->
<!--Based on XBRL 2.1-->
<!--Created on: 11/8/2023 7:48:33 PM-->
<!--Modified on: 11/8/2023 7:48:33 PM-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" roleURI="http://www.rhythmtx.com/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#StatementCondensedConsolidatedStatementsOfStockholdersEquity" roleURI="http://www.rhythmtx.com/role/StatementCondensedConsolidatedStatementsOfStockholdersEquity" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureSummaryOfSignificantAccountingPoliciesDetails" roleURI="http://www.rhythmtx.com/role/DisclosureSummaryOfSignificantAccountingPoliciesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureSummaryOfSignificantAccountingPoliciesLicenseAgreementsDetails" roleURI="http://www.rhythmtx.com/role/DisclosureSummaryOfSignificantAccountingPoliciesLicenseAgreementsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureSummaryOfSignificantAccountingPoliciesNetLossPerShareDetails" roleURI="http://www.rhythmtx.com/role/DisclosureSummaryOfSignificantAccountingPoliciesNetLossPerShareDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureAssetAcquisitionDetails" roleURI="http://www.rhythmtx.com/role/DisclosureAssetAcquisitionDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureFairValueOfFinancialAssetsAndLiabilitiesDetails" roleURI="http://www.rhythmtx.com/role/DisclosureFairValueOfFinancialAssetsAndLiabilitiesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureFairValueOfFinancialAssetsAndLiabilitiesChangesInLevel3SecuritiesDetails" roleURI="http://www.rhythmtx.com/role/DisclosureFairValueOfFinancialAssetsAndLiabilitiesChangesInLevel3SecuritiesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureFairValueOfFinancialAssetsAndLiabilitiesChangesInEmbeddedDerivativeLiabilityDetails" roleURI="http://www.rhythmtx.com/role/DisclosureFairValueOfFinancialAssetsAndLiabilitiesChangesInEmbeddedDerivativeLiabilityDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureFairValueOfFinancialAssetsAndLiabilitiesMarketableSecuritiesDetails" roleURI="http://www.rhythmtx.com/role/DisclosureFairValueOfFinancialAssetsAndLiabilitiesMarketableSecuritiesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureIntangibleAssetsDetails" roleURI="http://www.rhythmtx.com/role/DisclosureIntangibleAssetsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureIntangibleAssetsAmortizationExpenseDetails" roleURI="http://www.rhythmtx.com/role/DisclosureIntangibleAssetsAmortizationExpenseDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureCommonStockDetails" roleURI="http://www.rhythmtx.com/role/DisclosureCommonStockDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="rytm-20230930.xsd#DisclosureLongTermObligationsDetails" roleURI="http://www.rhythmtx.com/role/DisclosureLongTermObligationsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <link:arcroleRef arcroleURI="http://www.esma.europa.eu/xbrl/esef/arcrole/wider-narrower" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/arcrole/esma-arcrole-2018-11-21.xsd#wider-narrower" />
  <link:roleRef roleURI="http://www.rhythmtx.com/role/DisclosureStandardAndCustomAxisDomainDefaults" xlink:href="rytm-20230930.xsd#DisclosureStandardAndCustomAxisDomainDefaults" xlink:type="simple" />
  <roleRef xlink:type="simple" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-roles-2023.xsd#eedm" roleURI="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xmlns="http://www.xbrl.org/2003/linkbase" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all" xlink:type="simple" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain" xlink:type="simple" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member" xlink:type="simple" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension" xlink:type="simple" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default" xlink:type="simple" />
  <definitionLink xlink:role="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="extended" xlink:title="Extensible Enumeration Domain Members" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LiabilitiesAbstract" xlink:label="us-gaap_LiabilitiesAbstract" xlink:title="us-gaap_LiabilitiesAbstract" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent" xlink:title="us-gaap_OperatingLeaseLiabilityCurrent" />
    <definitionArc xlink:type="arc" xlink:from="us-gaap_LiabilitiesAbstract" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:title="definition:us-gaap_LiabilitiesAbstract To us-gaap_OperatingLeaseLiabilityCurrent" order="1" priority="0" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:title="us-gaap_OperatingLeaseLiabilityNoncurrent" />
    <definitionArc xlink:type="arc" xlink:from="us-gaap_LiabilitiesAbstract" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:title="definition:us-gaap_LiabilitiesAbstract To us-gaap_OperatingLeaseLiabilityNoncurrent" order="2" priority="0" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementAbstract" xlink:label="us-gaap_IncomeStatementAbstract" xlink:title="us-gaap_IncomeStatementAbstract" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="us-gaap_OtherNonoperatingIncomeExpense_1" xlink:title="us-gaap_OtherNonoperatingIncomeExpense_1" />
    <definitionArc xlink:type="arc" xlink:from="us-gaap_IncomeStatementAbstract" xlink:to="us-gaap_OtherNonoperatingIncomeExpense_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:title="definition:us-gaap_IncomeStatementAbstract To us-gaap_OtherNonoperatingIncomeExpense_1" order="1" priority="0" />
  </definitionLink>
  <link:definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureStandardAndCustomAxisDomainDefaults" xlink:type="extended" xlink:title="99900 - Disclosure - Standard And Custom Axis Domain Defaults">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="us-gaap_StatementEquityComponentsAxis_1" xlink:title="us-gaap_StatementEquityComponentsAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain_1" xlink:title="us-gaap_EquityComponentDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_StatementEquityComponentsAxis_1" xlink:to="us-gaap_EquityComponentDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_StatementEquityComponentsAxis_1 To us-gaap_EquityComponentDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CumulativeEffectPeriodOfAdoptionAxis" xlink:label="srt_CumulativeEffectPeriodOfAdoptionAxis_1" xlink:title="srt_CumulativeEffectPeriodOfAdoptionAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CumulativeEffectPeriodOfAdoptionDomain" xlink:label="srt_CumulativeEffectPeriodOfAdoptionDomain_1" xlink:title="srt_CumulativeEffectPeriodOfAdoptionDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_CumulativeEffectPeriodOfAdoptionAxis_1" xlink:to="srt_CumulativeEffectPeriodOfAdoptionDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_CumulativeEffectPeriodOfAdoptionAxis_1 To srt_CumulativeEffectPeriodOfAdoptionDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="us-gaap_BalanceSheetLocationAxis_1" xlink:title="us-gaap_BalanceSheetLocationAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="us-gaap_BalanceSheetLocationDomain_1" xlink:title="us-gaap_BalanceSheetLocationDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_BalanceSheetLocationAxis_1" xlink:to="us-gaap_BalanceSheetLocationDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_BalanceSheetLocationAxis_1 To us-gaap_BalanceSheetLocationDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_1" xlink:title="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AntidilutiveSecuritiesNameDomain" xlink:label="us-gaap_AntidilutiveSecuritiesNameDomain_1" xlink:title="us-gaap_AntidilutiveSecuritiesNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_1" xlink:to="us-gaap_AntidilutiveSecuritiesNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_1 To us-gaap_AntidilutiveSecuritiesNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByMeasurementFrequencyAxis" xlink:label="us-gaap_FairValueByMeasurementFrequencyAxis_1" xlink:title="us-gaap_FairValueByMeasurementFrequencyAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="us-gaap_FairValueMeasurementFrequencyDomain_1" xlink:title="us-gaap_FairValueMeasurementFrequencyDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_FairValueByMeasurementFrequencyAxis_1" xlink:to="us-gaap_FairValueMeasurementFrequencyDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_FairValueByMeasurementFrequencyAxis_1 To us-gaap_FairValueMeasurementFrequencyDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis_1" xlink:title="us-gaap_FairValueByFairValueHierarchyLevelAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" xlink:title="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis_1" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_FairValueByFairValueHierarchyLevelAxis_1 To us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="us-gaap_FinancialInstrumentAxis_1" xlink:title="us-gaap_FinancialInstrumentAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1" xlink:title="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_FinancialInstrumentAxis_1" xlink:to="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_FinancialInstrumentAxis_1 To us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByLiabilityClassAxis" xlink:label="us-gaap_FairValueByLiabilityClassAxis_1" xlink:title="us-gaap_FairValueByLiabilityClassAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain" xlink:label="us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_1" xlink:title="us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_FairValueByLiabilityClassAxis_1" xlink:to="us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_FairValueByLiabilityClassAxis_1 To us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByMeasurementBasisAxis" xlink:label="us-gaap_FairValueByMeasurementBasisAxis_1" xlink:title="us-gaap_FairValueByMeasurementBasisAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PortionAtFairValueFairValueDisclosureMember" xlink:label="us-gaap_PortionAtFairValueFairValueDisclosureMember_1" xlink:title="us-gaap_PortionAtFairValueFairValueDisclosureMember_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_FairValueByMeasurementBasisAxis_1" xlink:to="us-gaap_PortionAtFairValueFairValueDisclosureMember_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_FairValueByMeasurementBasisAxis_1 To us-gaap_PortionAtFairValueFairValueDisclosureMember_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameAxis" xlink:label="us-gaap_PlanNameAxis_1" xlink:title="us-gaap_PlanNameAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain" xlink:label="us-gaap_PlanNameDomain_1" xlink:title="us-gaap_PlanNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_PlanNameAxis_1" xlink:to="us-gaap_PlanNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_PlanNameAxis_1 To us-gaap_PlanNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis_1" xlink:title="us-gaap_AwardTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" xlink:title="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_AwardTypeAxis_1" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_AwardTypeAxis_1 To us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis_1" xlink:title="us-gaap_TypeOfArrangementAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" xlink:title="us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_TypeOfArrangementAxis_1" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_TypeOfArrangementAxis_1 To us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis_1" xlink:title="srt_CounterpartyNameAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain_1" xlink:title="srt_RepurchaseAgreementCounterpartyNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_CounterpartyNameAxis_1" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_CounterpartyNameAxis_1 To srt_RepurchaseAgreementCounterpartyNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_TitleOfIndividualAxis" xlink:label="srt_TitleOfIndividualAxis_1" xlink:title="srt_TitleOfIndividualAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain" xlink:label="srt_TitleOfIndividualWithRelationshipToEntityDomain_1" xlink:title="srt_TitleOfIndividualWithRelationshipToEntityDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_TitleOfIndividualAxis_1" xlink:to="srt_TitleOfIndividualWithRelationshipToEntityDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_TitleOfIndividualAxis_1 To srt_TitleOfIndividualWithRelationshipToEntityDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis_1" xlink:title="srt_RangeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember" xlink:label="srt_RangeMember_1" xlink:title="srt_RangeMember_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_RangeAxis_1" xlink:to="srt_RangeMember_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_RangeAxis_1 To srt_RangeMember_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementClassOfStockAxis" xlink:label="us-gaap_StatementClassOfStockAxis_1" xlink:title="us-gaap_StatementClassOfStockAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfStockDomain" xlink:label="us-gaap_ClassOfStockDomain_1" xlink:title="us-gaap_ClassOfStockDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_StatementClassOfStockAxis_1" xlink:to="us-gaap_ClassOfStockDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_StatementClassOfStockAxis_1 To us-gaap_ClassOfStockDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis_1" xlink:title="us-gaap_SubsidiarySaleOfStockAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain_1" xlink:title="us-gaap_SaleOfStockNameOfTransactionDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_SubsidiarySaleOfStockAxis_1" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_SubsidiarySaleOfStockAxis_1 To us-gaap_SaleOfStockNameOfTransactionDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1" xlink:title="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RelatedPartyDomain" xlink:label="us-gaap_RelatedPartyDomain_1" xlink:title="us-gaap_RelatedPartyDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1" xlink:to="us-gaap_RelatedPartyDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1 To us-gaap_RelatedPartyDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GranteeStatusAxis" xlink:label="us-gaap_GranteeStatusAxis_1" xlink:title="us-gaap_GranteeStatusAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GranteeStatusDomain" xlink:label="us-gaap_GranteeStatusDomain_1" xlink:title="us-gaap_GranteeStatusDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_GranteeStatusAxis_1" xlink:to="us-gaap_GranteeStatusDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_GranteeStatusAxis_1 To us-gaap_GranteeStatusDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis_1" xlink:title="us-gaap_PropertyPlantAndEquipmentByTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain_1" xlink:title="us-gaap_PropertyPlantAndEquipmentTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_PropertyPlantAndEquipmentByTypeAxis_1" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_PropertyPlantAndEquipmentByTypeAxis_1 To us-gaap_PropertyPlantAndEquipmentTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis_1" xlink:title="srt_ProductOrServiceAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain_1" xlink:title="srt_ProductsAndServicesDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_ProductOrServiceAxis_1" xlink:to="srt_ProductsAndServicesDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_ProductOrServiceAxis_1 To srt_ProductsAndServicesDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis_1" xlink:title="us-gaap_IncomeStatementLocationAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain_1" xlink:title="us-gaap_IncomeStatementLocationDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_IncomeStatementLocationAxis_1" xlink:to="us-gaap_IncomeStatementLocationDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_IncomeStatementLocationAxis_1 To us-gaap_IncomeStatementLocationDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_StatementScenarioAxis" xlink:label="srt_StatementScenarioAxis_1" xlink:title="srt_StatementScenarioAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="srt_ScenarioUnspecifiedDomain_1" xlink:title="srt_ScenarioUnspecifiedDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_StatementScenarioAxis_1" xlink:to="srt_ScenarioUnspecifiedDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_StatementScenarioAxis_1 To srt_ScenarioUnspecifiedDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_1" xlink:title="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain" xlink:label="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_1" xlink:title="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_1" xlink:to="us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_1 To us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TaxCreditCarryforwardAxis" xlink:label="us-gaap_TaxCreditCarryforwardAxis_1" xlink:title="us-gaap_TaxCreditCarryforwardAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TaxCreditCarryforwardNameDomain" xlink:label="us-gaap_TaxCreditCarryforwardNameDomain_1" xlink:title="us-gaap_TaxCreditCarryforwardNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_TaxCreditCarryforwardAxis_1" xlink:to="us-gaap_TaxCreditCarryforwardNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_TaxCreditCarryforwardAxis_1 To us-gaap_TaxCreditCarryforwardNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxAuthorityAxis" xlink:label="us-gaap_IncomeTaxAuthorityAxis_1" xlink:title="us-gaap_IncomeTaxAuthorityAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxAuthorityDomain" xlink:label="us-gaap_IncomeTaxAuthorityDomain_1" xlink:title="us-gaap_IncomeTaxAuthorityDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_IncomeTaxAuthorityAxis_1" xlink:to="us-gaap_IncomeTaxAuthorityDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_IncomeTaxAuthorityAxis_1 To us-gaap_IncomeTaxAuthorityDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="us-gaap_SubsequentEventTypeAxis_1" xlink:title="us-gaap_SubsequentEventTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="us-gaap_SubsequentEventTypeDomain_1" xlink:title="us-gaap_SubsequentEventTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_SubsequentEventTypeAxis_1" xlink:to="us-gaap_SubsequentEventTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_SubsequentEventTypeAxis_1 To us-gaap_SubsequentEventTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis_1" xlink:title="us-gaap_DebtInstrumentAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain_1" xlink:title="us-gaap_DebtInstrumentNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_DebtInstrumentAxis_1" xlink:to="us-gaap_DebtInstrumentNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_DebtInstrumentAxis_1 To us-gaap_DebtInstrumentNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="us-gaap_ConcentrationRiskByTypeAxis_1" xlink:title="us-gaap_ConcentrationRiskByTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="us-gaap_ConcentrationRiskTypeDomain_1" xlink:title="us-gaap_ConcentrationRiskTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_ConcentrationRiskByTypeAxis_1" xlink:to="us-gaap_ConcentrationRiskTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_ConcentrationRiskByTypeAxis_1 To us-gaap_ConcentrationRiskTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MajorCustomersAxis" xlink:label="srt_MajorCustomersAxis_1" xlink:title="srt_MajorCustomersAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_NameOfMajorCustomerDomain" xlink:label="srt_NameOfMajorCustomerDomain_1" xlink:title="srt_NameOfMajorCustomerDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_MajorCustomersAxis_1" xlink:to="srt_NameOfMajorCustomerDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_MajorCustomersAxis_1 To srt_NameOfMajorCustomerDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="us-gaap_ConcentrationRiskByBenchmarkAxis_1" xlink:title="us-gaap_ConcentrationRiskByBenchmarkAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="us-gaap_ConcentrationRiskBenchmarkDomain_1" xlink:title="us-gaap_ConcentrationRiskBenchmarkDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_ConcentrationRiskByBenchmarkAxis_1" xlink:to="us-gaap_ConcentrationRiskBenchmarkDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_ConcentrationRiskByBenchmarkAxis_1 To us-gaap_ConcentrationRiskBenchmarkDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_1" xlink:title="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_1" xlink:title="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_1" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_1 To us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinancingReceivableRecordedInvestmentByClassOfFinancingReceivableAxis" xlink:label="us-gaap_FinancingReceivableRecordedInvestmentByClassOfFinancingReceivableAxis_1" xlink:title="us-gaap_FinancingReceivableRecordedInvestmentByClassOfFinancingReceivableAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinancingReceivableRecordedInvestmentClassOfFinancingReceivableDomain" xlink:label="us-gaap_FinancingReceivableRecordedInvestmentClassOfFinancingReceivableDomain_1" xlink:title="us-gaap_FinancingReceivableRecordedInvestmentClassOfFinancingReceivableDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_FinancingReceivableRecordedInvestmentByClassOfFinancingReceivableAxis_1" xlink:to="us-gaap_FinancingReceivableRecordedInvestmentClassOfFinancingReceivableDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_FinancingReceivableRecordedInvestmentByClassOfFinancingReceivableAxis_1 To us-gaap_FinancingReceivableRecordedInvestmentClassOfFinancingReceivableDomain_1" order="1" />
  </link:definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" xlink:type="extended" xlink:title="00200 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="srt_ProductOrServiceAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProductMember" xlink:label="us-gaap_ProductMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_ProductMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LicenseMember" xlink:label="us-gaap_LicenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_LicenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="us-gaap_CostsAndExpensesAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CostsAndExpensesAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="us-gaap_CostOfGoodsAndServicesSold" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_CostsAndExpensesAbstract" xlink:to="us-gaap_CostOfGoodsAndServicesSold" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:label="us-gaap_ResearchAndDevelopmentExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CostsAndExpensesAbstract" xlink:to="us-gaap_ResearchAndDevelopmentExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SellingGeneralAndAdministrativeExpense" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_CostsAndExpensesAbstract" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CostsAndExpenses" xlink:label="us-gaap_CostsAndExpenses" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpenses" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingIncomeLoss" xlink:label="us-gaap_OperatingIncomeLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OperatingIncomeLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NonoperatingIncomeExpenseAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="us-gaap_OtherNonoperatingIncomeExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_OtherNonoperatingIncomeExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InterestExpense" xlink:label="us-gaap_InterestExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_InterestExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InvestmentIncomeNet" xlink:label="us-gaap_InvestmentIncomeNet" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_InvestmentIncomeNet" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NonoperatingIncomeExpense" xlink:label="us-gaap_NonoperatingIncomeExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_NonoperatingIncomeExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="us-gaap_IncomeTaxExpenseBenefit" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_IncomeTaxExpenseBenefit" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetIncomeLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EarningsPerShareBasic" xlink:label="us-gaap_EarningsPerShareBasic" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EarningsPerShareBasic" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EarningsPerShareDiluted" xlink:label="us-gaap_EarningsPerShareDiluted" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EarningsPerShareDiluted" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract" xlink:label="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="13" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_ReclassificationOfLosses" xlink:label="rytm_ReclassificationOfLosses" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract" xlink:to="rytm_ReclassificationOfLosses" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract" xlink:to="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract" xlink:to="us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract" xlink:to="us-gaap_ComprehensiveIncomeNetOfTax" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/StatementCondensedConsolidatedStatementsOfStockholdersEquity" xlink:type="extended" xlink:title="00300 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="us-gaap_StatementEquityComponentsAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_StatementEquityComponentsAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockMember" xlink:label="us-gaap_CommonStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_CommonStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:label="us-gaap_AdditionalPaidInCapitalMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AdditionalPaidInCapitalMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RetainedEarningsMember" xlink:label="us-gaap_RetainedEarningsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_RetainedEarningsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_AtMarketOfferingsMember" xlink:label="rytm_AtMarketOfferingsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="rytm_AtMarketOfferingsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_StatementTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_RareStoneGroupLtdMember" xlink:label="rytm_RareStoneGroupLtdMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="rytm_RareStoneGroupLtdMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:label="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_StockholdersEquity" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharesOutstanding" xlink:label="us-gaap_SharesOutstanding" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_SharesOutstanding" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan" xlink:label="us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" xlink:label="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan" xlink:to="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_StockIssuedDuringPeriodValueStockOptionsAndRestrictedStockUnitsVesting" xlink:label="rytm_StockIssuedDuringPeriodValueStockOptionsAndRestrictedStockUnitsVesting" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="rytm_StockIssuedDuringPeriodValueStockOptionsAndRestrictedStockUnitsVesting" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_StockIssuedDuringPeriodSharesStockOptionsAndRestrictedStockUnitsVesting" xlink:label="rytm_StockIssuedDuringPeriodSharesStockOptionsAndRestrictedStockUnitsVesting" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="rytm_StockIssuedDuringPeriodValueStockOptionsAndRestrictedStockUnitsVesting" xlink:to="rytm_StockIssuedDuringPeriodSharesStockOptionsAndRestrictedStockUnitsVesting" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtAndEquitySecuritiesGainLoss" xlink:label="us-gaap_DebtAndEquitySecuritiesGainLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_DebtAndEquitySecuritiesGainLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" xlink:label="us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" xlink:label="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" xlink:to="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_MarketableSecuritiesUnrealizedGainLoss" xlink:label="us-gaap_MarketableSecuritiesUnrealizedGainLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_MarketableSecuritiesUnrealizedGainLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_RarestoneValuationUnrealizedGainLoss" xlink:label="rytm_RarestoneValuationUnrealizedGainLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="rytm_RarestoneValuationUnrealizedGainLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GainLossOnContractTermination" xlink:label="us-gaap_GainLossOnContractTermination" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_GainLossOnContractTermination" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="13" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_NetIncomeLoss" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureSummaryOfSignificantAccountingPoliciesDetails" xlink:type="extended" xlink:title="40201 - Disclosure - Summary of Significant Accounting Policies (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InventoryCurrentTable" xlink:label="us-gaap_InventoryCurrentTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="us-gaap_BalanceSheetLocationAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_InventoryCurrentTable" xlink:to="us-gaap_BalanceSheetLocationAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="us-gaap_BalanceSheetLocationDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_BalanceSheetLocationAxis" xlink:to="us-gaap_BalanceSheetLocationDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccountsReceivableMember" xlink:label="us-gaap_AccountsReceivableMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_BalanceSheetLocationDomain" xlink:to="us-gaap_AccountsReceivableMember" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_InventoryMember" xlink:label="rytm_InventoryMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_BalanceSheetLocationDomain" xlink:to="rytm_InventoryMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_InventoryCurrentTable" xlink:to="srt_ProductOrServiceAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProductMember" xlink:label="us-gaap_ProductMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_ProductMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="us-gaap_ConcentrationRiskByTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_InventoryCurrentTable" xlink:to="us-gaap_ConcentrationRiskByTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="us-gaap_ConcentrationRiskTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_ConcentrationRiskByTypeAxis" xlink:to="us-gaap_ConcentrationRiskTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CustomerConcentrationRiskMember" xlink:label="us-gaap_CustomerConcentrationRiskMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ConcentrationRiskTypeDomain" xlink:to="us-gaap_CustomerConcentrationRiskMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MajorCustomersAxis" xlink:label="srt_MajorCustomersAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_InventoryCurrentTable" xlink:to="srt_MajorCustomersAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_NameOfMajorCustomerDomain" xlink:label="srt_NameOfMajorCustomerDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_MajorCustomersAxis" xlink:to="srt_NameOfMajorCustomerDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_CustomerOneMember" xlink:label="rytm_CustomerOneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_NameOfMajorCustomerDomain" xlink:to="rytm_CustomerOneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="us-gaap_ConcentrationRiskByBenchmarkAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="5" xlink:from="us-gaap_InventoryCurrentTable" xlink:to="us-gaap_ConcentrationRiskByBenchmarkAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="us-gaap_ConcentrationRiskBenchmarkDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:to="us-gaap_ConcentrationRiskBenchmarkDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SalesRevenueNetMember" xlink:label="us-gaap_SalesRevenueNetMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ConcentrationRiskBenchmarkDomain" xlink:to="us-gaap_SalesRevenueNetMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InventoryLineItems" xlink:label="us-gaap_InventoryLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_InventoryLineItems" xlink:to="us-gaap_InventoryCurrentTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PriorPeriodReclassificationAdjustment" xlink:label="us-gaap_PriorPeriodReclassificationAdjustment" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_InventoryLineItems" xlink:to="us-gaap_PriorPeriodReclassificationAdjustment" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:label="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_InventoryLineItems" xlink:to="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NumberOfOperatingSegments" xlink:label="us-gaap_NumberOfOperatingSegments" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:to="us-gaap_NumberOfOperatingSegments" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NumberOfReportableSegments" xlink:label="us-gaap_NumberOfReportableSegments" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:to="us-gaap_NumberOfReportableSegments" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_OffBalanceSheetRiskAndConcentrationsOfCreditRiskAbstract" xlink:label="rytm_OffBalanceSheetRiskAndConcentrationsOfCreditRiskAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_InventoryLineItems" xlink:to="rytm_OffBalanceSheetRiskAndConcentrationsOfCreditRiskAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_NumberOfFederallyInsuredFinancialInstitutions" xlink:label="rytm_NumberOfFederallyInsuredFinancialInstitutions" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="rytm_OffBalanceSheetRiskAndConcentrationsOfCreditRiskAbstract" xlink:to="rytm_NumberOfFederallyInsuredFinancialInstitutions" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="us-gaap_ConcentrationRiskPercentage1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="rytm_OffBalanceSheetRiskAndConcentrationsOfCreditRiskAbstract" xlink:to="us-gaap_ConcentrationRiskPercentage1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TangibleAssetImpairmentChargesAbstract" xlink:label="us-gaap_TangibleAssetImpairmentChargesAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_InventoryLineItems" xlink:to="us-gaap_TangibleAssetImpairmentChargesAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TangibleAssetImpairmentCharges" xlink:label="us-gaap_TangibleAssetImpairmentCharges" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_TangibleAssetImpairmentChargesAbstract" xlink:to="us-gaap_TangibleAssetImpairmentCharges" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ReceivablesNetCurrentAbstract" xlink:label="us-gaap_ReceivablesNetCurrentAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_InventoryLineItems" xlink:to="us-gaap_ReceivablesNetCurrentAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ReceivablesNetCurrent" xlink:label="us-gaap_ReceivablesNetCurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ReceivablesNetCurrentAbstract" xlink:to="us-gaap_ReceivablesNetCurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_InventoryLineItems" xlink:to="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureSummaryOfSignificantAccountingPoliciesLicenseAgreementsDetails" xlink:type="extended" xlink:title="40202 - Disclosure - Summary of Significant Accounting Policies - License Agreements (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_RareStoneGroupLtdMember" xlink:label="rytm_RareStoneGroupLtdMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="rytm_RareStoneGroupLtdMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_LicenseAgreementMember" xlink:label="rytm_LicenseAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="rytm_LicenseAgreementMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_LicenseAgreementNumberOfPerformanceObligations" xlink:label="rytm_LicenseAgreementNumberOfPerformanceObligations" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="rytm_LicenseAgreementNumberOfPerformanceObligations" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_LicenseAgreementCommercialManufacturingSupplyDiscount" xlink:label="rytm_LicenseAgreementCommercialManufacturingSupplyDiscount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="rytm_LicenseAgreementCommercialManufacturingSupplyDiscount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_RarestoneValuationRealizedGainLoss" xlink:label="rytm_RarestoneValuationRealizedGainLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="rytm_RarestoneValuationRealizedGainLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GainLossOnContractTermination" xlink:label="us-gaap_GainLossOnContractTermination" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_GainLossOnContractTermination" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_LicenseAgreementUpfrontConsideration" xlink:label="rytm_LicenseAgreementUpfrontConsideration" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="rytm_LicenseAgreementUpfrontConsideration" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_NumberOfIndependentSubStudiesInPatients" xlink:label="rytm_NumberOfIndependentSubStudiesInPatients" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="rytm_NumberOfIndependentSubStudiesInPatients" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_UpfrontPayment" xlink:label="rytm_UpfrontPayment" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="rytm_UpfrontPayment" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherAssetsFairValueDisclosure" xlink:label="us-gaap_OtherAssetsFairValueDisclosure" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_OtherAssetsFairValueDisclosure" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_AggregatePaymentUponAchievementOfDevelopmentAndCommercialMilestones" xlink:label="rytm_AggregatePaymentUponAchievementOfDevelopmentAndCommercialMilestones" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="rytm_AggregatePaymentUponAchievementOfDevelopmentAndCommercialMilestones" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_StockIssuedDuringPeriodSharesNewIssuesLicenseAgreement" xlink:label="rytm_StockIssuedDuringPeriodSharesNewIssuesLicenseAgreement" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="rytm_StockIssuedDuringPeriodSharesNewIssuesLicenseAgreement" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureSummaryOfSignificantAccountingPoliciesNetLossPerShareDetails" xlink:type="extended" xlink:title="40203 - Disclosure - Summary of Significant Accounting Policies - Net loss per share (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" xlink:label="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" xlink:to="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AntidilutiveSecuritiesNameDomain" xlink:label="us-gaap_AntidilutiveSecuritiesNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:to="us-gaap_AntidilutiveSecuritiesNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_AntidilutiveSecuritiesNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedStockUnitsRSUMember" xlink:label="us-gaap_RestrictedStockUnitsRSUMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AntidilutiveSecuritiesNameDomain" xlink:to="us-gaap_RestrictedStockUnitsRSUMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PerformanceSharesMember" xlink:label="us-gaap_PerformanceSharesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_AntidilutiveSecuritiesNameDomain" xlink:to="us-gaap_PerformanceSharesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:to="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:to="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureAssetAcquisitionDetails" xlink:type="extended" xlink:title="40301 - Disclosure - Asset Acquisition (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetAcquisitionTable" xlink:label="us-gaap_AssetAcquisitionTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_AssetAcquisitionTable" xlink:to="us-gaap_IncomeStatementLocationAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentExpenseMember" xlink:label="us-gaap_ResearchAndDevelopmentExpenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_ResearchAndDevelopmentExpenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_AssetAcquisitionTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_XinventoBVMember" xlink:label="rytm_XinventoBVMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="rytm_XinventoBVMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetAcquisitionLineItems" xlink:label="us-gaap_AssetAcquisitionLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_AssetAcquisitionLineItems" xlink:to="us-gaap_AssetAcquisitionTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_AggregatePaymentUponAchievementOfDevelopmentAndCommercialMilestones" xlink:label="rytm_AggregatePaymentUponAchievementOfDevelopmentAndCommercialMilestones" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AssetAcquisitionLineItems" xlink:to="rytm_AggregatePaymentUponAchievementOfDevelopmentAndCommercialMilestones" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_ClinicalDevelopmentMilestonePayments" xlink:label="rytm_ClinicalDevelopmentMilestonePayments" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_AssetAcquisitionLineItems" xlink:to="rytm_ClinicalDevelopmentMilestonePayments" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_CommercialRegulatoryApprovalAndMilestonePayments" xlink:label="rytm_CommercialRegulatoryApprovalAndMilestonePayments" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_AssetAcquisitionLineItems" xlink:to="rytm_CommercialRegulatoryApprovalAndMilestonePayments" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_SalesMilestonePayments" xlink:label="rytm_SalesMilestonePayments" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_AssetAcquisitionLineItems" xlink:to="rytm_SalesMilestonePayments" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BusinessCombinationConsiderationTransferred1" xlink:label="us-gaap_BusinessCombinationConsiderationTransferred1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_AssetAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationConsiderationTransferred1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentsToAcquireBusinessesGross" xlink:label="us-gaap_PaymentsToAcquireBusinessesGross" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_AssetAcquisitionLineItems" xlink:to="us-gaap_PaymentsToAcquireBusinessesGross" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_HoldbackPayableOnOneYearAnniversaryOfAcquisition" xlink:label="rytm_HoldbackPayableOnOneYearAnniversaryOfAcquisition" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_AssetAcquisitionLineItems" xlink:to="rytm_HoldbackPayableOnOneYearAnniversaryOfAcquisition" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BusinessCombinationAcquisitionRelatedCosts" xlink:label="us-gaap_BusinessCombinationAcquisitionRelatedCosts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_AssetAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationAcquisitionRelatedCosts" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureFairValueOfFinancialAssetsAndLiabilitiesDetails" xlink:type="extended" xlink:title="40601 - Disclosure - Fair Value of Financial Assets and Liabilities (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByMeasurementFrequencyAxis" xlink:label="us-gaap_FairValueByMeasurementFrequencyAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByMeasurementFrequencyAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="us-gaap_FairValueMeasurementFrequencyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByMeasurementFrequencyAxis" xlink:to="us-gaap_FairValueMeasurementFrequencyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsRecurringMember" xlink:label="us-gaap_FairValueMeasurementsRecurringMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueMeasurementFrequencyDomain" xlink:to="us-gaap_FairValueMeasurementsRecurringMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel1Member" xlink:label="us-gaap_FairValueInputsLevel1Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel1Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel2Member" xlink:label="us-gaap_FairValueInputsLevel2Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel2Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel3Member" xlink:label="us-gaap_FairValueInputsLevel3Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel3Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="us-gaap_FinancialInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FinancialInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FinancialInstrumentAxis" xlink:to="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommercialPaperMember" xlink:label="us-gaap_CommercialPaperMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="us-gaap_CommercialPaperMember" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_CorporateDebtSecuritiesAndCommercialPaperMember" xlink:label="rytm_CorporateDebtSecuritiesAndCommercialPaperMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="rytm_CorporateDebtSecuritiesAndCommercialPaperMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_MoneyMarketFundsMember" xlink:label="us-gaap_MoneyMarketFundsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="us-gaap_MoneyMarketFundsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByLiabilityClassAxis" xlink:label="us-gaap_FairValueByLiabilityClassAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByLiabilityClassAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain" xlink:label="us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByLiabilityClassAxis" xlink:to="us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DerivativeFinancialInstrumentsLiabilitiesMember" xlink:label="us-gaap_DerivativeFinancialInstrumentsLiabilitiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain" xlink:to="us-gaap_DerivativeFinancialInstrumentsLiabilitiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByMeasurementBasisAxis" xlink:label="us-gaap_FairValueByMeasurementBasisAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="5" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByMeasurementBasisAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PortionAtFairValueFairValueDisclosureMember" xlink:label="us-gaap_PortionAtFairValueFairValueDisclosureMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByMeasurementBasisAxis" xlink:to="us-gaap_PortionAtFairValueFairValueDisclosureMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EstimateOfFairValueFairValueDisclosureMember" xlink:label="us-gaap_EstimateOfFairValueFairValueDisclosureMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PortionAtFairValueFairValueDisclosureMember" xlink:to="us-gaap_EstimateOfFairValueFairValueDisclosureMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CashCashEquivalentsAndShortTermInvestments" xlink:label="us-gaap_CashCashEquivalentsAndShortTermInvestments" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_CashCashEquivalentsAndShortTermInvestments" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetsFairValueDisclosureAbstract" xlink:label="us-gaap_AssetsFairValueDisclosureAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AssetsFairValueDisclosureAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_AssetsFairValueDisclosureAbstract" xlink:to="us-gaap_CashAndCashEquivalentsFairValueDisclosure" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AssetsFairValueDisclosureAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="us-gaap_AssetsFairValueDisclosure" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_AssetsFairValueDisclosureAbstract" xlink:to="us-gaap_AssetsFairValueDisclosure" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DerivativeLiabilities" xlink:label="us-gaap_DerivativeLiabilities" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_AssetsFairValueDisclosureAbstract" xlink:to="us-gaap_DerivativeLiabilities" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureFairValueOfFinancialAssetsAndLiabilitiesChangesInLevel3SecuritiesDetails" xlink:type="extended" xlink:title="40602 - Disclosure - Fair Value of Financial Assets and Liabilities - Changes in Level 3 Securities (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel3Member" xlink:label="us-gaap_FairValueInputsLevel3Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel3Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetPurchases" xlink:label="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetPurchases" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetPurchases" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetGainLossIncludedInEarnings1" xlink:label="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetGainLossIncludedInEarnings1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetGainLossIncludedInEarnings1" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureFairValueOfFinancialAssetsAndLiabilitiesChangesInEmbeddedDerivativeLiabilityDetails" xlink:type="extended" xlink:title="40603 - Disclosure - Fair Value of Financial Assets and Liabilities - Changes in Embedded Derivative Liability (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmbeddedDerivativeTable" xlink:label="us-gaap_EmbeddedDerivativeTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_EmbeddedDerivativeTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_RevenueInterestFinancingAgreementMember" xlink:label="rytm_RevenueInterestFinancingAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="rytm_RevenueInterestFinancingAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmbeddedDerivativeLineItems" xlink:label="us-gaap_EmbeddedDerivativeLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_EmbeddedDerivativeLineItems" xlink:to="us-gaap_EmbeddedDerivativeTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmbeddedDerivativeFairValueOfEmbeddedDerivativeLiability" xlink:label="us-gaap_EmbeddedDerivativeFairValueOfEmbeddedDerivativeLiability" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_EmbeddedDerivativeLineItems" xlink:to="us-gaap_EmbeddedDerivativeFairValueOfEmbeddedDerivativeLiability" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmbeddedDerivativeGainLossOnEmbeddedDerivativeNet" xlink:label="us-gaap_EmbeddedDerivativeGainLossOnEmbeddedDerivativeNet" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_EmbeddedDerivativeLineItems" xlink:to="us-gaap_EmbeddedDerivativeGainLossOnEmbeddedDerivativeNet" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureFairValueOfFinancialAssetsAndLiabilitiesMarketableSecuritiesDetails" xlink:type="extended" xlink:title="40604 - Disclosure - Fair Value of Financial Assets and Liabilities - Marketable Securities (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="us-gaap_FinancialInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FinancialInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FinancialInstrumentAxis" xlink:to="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_CorporateDebtSecuritiesAndCommercialPaperMember" xlink:label="rytm_CorporateDebtSecuritiesAndCommercialPaperMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="rytm_CorporateDebtSecuritiesAndCommercialPaperMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureIntangibleAssetsDetails" xlink:type="extended" xlink:title="40801 - Disclosure - Intangible Assets (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" xlink:label="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_CapitalizedMilestonesMember" xlink:label="rytm_CapitalizedMilestonesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="rytm_CapitalizedMilestonesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:label="us-gaap_FiniteLivedIntangibleAssetsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife" xlink:label="us-gaap_FiniteLivedIntangibleAssetUsefulLife" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetUsefulLife" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsGross" xlink:label="us-gaap_FiniteLivedIntangibleAssetsGross" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetsGross" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNet" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureIntangibleAssetsAmortizationExpenseDetails" xlink:type="extended" xlink:title="40802 - Disclosure - Intangible Assets - Amortization expense (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" xlink:label="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" xlink:to="us-gaap_IncomeStatementLocationAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CostOfSalesMember" xlink:label="us-gaap_CostOfSalesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_CostOfSalesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:label="us-gaap_FiniteLivedIntangibleAssetsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract" xlink:label="us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_FiniteLivedIntangibleAssetExpectedAmortizationAfterYearFour" xlink:label="rytm_FiniteLivedIntangibleAssetExpectedAmortizationAfterYearFour" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract" xlink:to="rytm_FiniteLivedIntangibleAssetExpectedAmortizationAfterYearFour" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_FiniteLivedIntangibleAssetsFutureAmortizationExpenseAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNet" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AmortizationOfIntangibleAssets" xlink:label="us-gaap_AmortizationOfIntangibleAssets" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_FiniteLivedIntangibleAssetsLineItems" xlink:to="us-gaap_AmortizationOfIntangibleAssets" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureCommonStockDetails" xlink:type="extended" xlink:title="41001 - Disclosure - Common Stock (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfStockByClassTable" xlink:label="us-gaap_ScheduleOfStockByClassTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfStockByClassTable" xlink:to="us-gaap_AwardTypeAxis" priority="4" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedStockUnitsRSUMember" xlink:label="us-gaap_RestrictedStockUnitsRSUMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_RestrictedStockUnitsRSUMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfStockByClassTable" xlink:to="srt_RangeAxis" priority="5" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember" xlink:label="srt_RangeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementClassOfStockAxis" xlink:label="us-gaap_StatementClassOfStockAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_ScheduleOfStockByClassTable" xlink:to="us-gaap_StatementClassOfStockAxis" priority="3" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfStockDomain" xlink:label="us-gaap_ClassOfStockDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_StatementClassOfStockAxis" xlink:to="us-gaap_ClassOfStockDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockMember" xlink:label="us-gaap_CommonStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ClassOfStockDomain" xlink:to="us-gaap_CommonStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PreferredStockMember" xlink:label="us-gaap_PreferredStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ClassOfStockDomain" xlink:to="us-gaap_PreferredStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockOptionMember" xlink:label="us-gaap_StockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PreferredStockMember" xlink:to="us-gaap_StockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_ScheduleOfStockByClassTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" priority="3" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_AtMarketOfferingsMember" xlink:label="rytm_AtMarketOfferingsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="rytm_AtMarketOfferingsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameAxis" xlink:label="us-gaap_PlanNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="5" xlink:from="us-gaap_ScheduleOfStockByClassTable" xlink:to="us-gaap_PlanNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain" xlink:label="us-gaap_PlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_PlanNameAxis" xlink:to="us-gaap_PlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_TwoThousandSeventeenEmployeeStockPurchasePlanMember" xlink:label="rytm_TwoThousandSeventeenEmployeeStockPurchasePlanMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PlanNameDomain" xlink:to="rytm_TwoThousandSeventeenEmployeeStockPurchasePlanMember" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_EmploymentInducementPlan2022Member" xlink:label="rytm_EmploymentInducementPlan2022Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_PlanNameDomain" xlink:to="rytm_EmploymentInducementPlan2022Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfStockLineItems" xlink:label="us-gaap_ClassOfStockLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_ScheduleOfStockByClassTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" xlink:label="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_ClassOfStockLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.rhythmtx.com/role/DisclosureLongTermObligationsDetails" xlink:type="extended" xlink:title="41201 - Disclosure - Long-Term Obligations (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentTable" xlink:label="us-gaap_DebtInstrumentTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_RevenueInterestFinancingAgreementMember" xlink:label="rytm_RevenueInterestFinancingAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="rytm_RevenueInterestFinancingAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="srt_RangeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember" xlink:label="srt_RangeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_RangeAxis" xlink:to="srt_RangeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MinimumMember" xlink:label="srt_MinimumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RangeMember" xlink:to="srt_MinimumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember" xlink:label="srt_MaximumMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RangeMember" xlink:to="srt_MaximumMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_StatementScenarioAxis" xlink:label="srt_StatementScenarioAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="srt_StatementScenarioAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="srt_ScenarioUnspecifiedDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_StatementScenarioAxis" xlink:to="srt_ScenarioUnspecifiedDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_AnnualNetRevenuesUpTo125MillionMember" xlink:label="rytm_AnnualNetRevenuesUpTo125MillionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ScenarioUnspecifiedDomain" xlink:to="rytm_AnnualNetRevenuesUpTo125MillionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_AnnualNetRevenuesBetween125MillionAnd300MillionMember" xlink:label="rytm_AnnualNetRevenuesBetween125MillionAnd300MillionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_ScenarioUnspecifiedDomain" xlink:to="rytm_AnnualNetRevenuesBetween125MillionAnd300MillionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_AnnualNetRevenuesExceeding300MillionMember" xlink:label="rytm_AnnualNetRevenuesExceeding300MillionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="srt_ScenarioUnspecifiedDomain" xlink:to="rytm_AnnualNetRevenuesExceeding300MillionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_CumulativeMinimumPaymentsFundingThresholdDateMarch312027Member" xlink:label="rytm_CumulativeMinimumPaymentsFundingThresholdDateMarch312027Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="srt_ScenarioUnspecifiedDomain" xlink:to="rytm_CumulativeMinimumPaymentsFundingThresholdDateMarch312027Member" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_CumulativeMinimumPaymentsFundingThresholdDateMarch312029Member" xlink:label="rytm_CumulativeMinimumPaymentsFundingThresholdDateMarch312029Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="srt_ScenarioUnspecifiedDomain" xlink:to="rytm_CumulativeMinimumPaymentsFundingThresholdDateMarch312029Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="us-gaap_DebtInstrumentLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="us-gaap_DebtInstrumentFaceAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentFaceAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_PercentOfRoyaltyInterestPaymentOnAnnualNetRevenues" xlink:label="rytm_PercentOfRoyaltyInterestPaymentOnAnnualNetRevenues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="rytm_PercentOfRoyaltyInterestPaymentOnAnnualNetRevenues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_ThresholdAnnualNetRevenuesForRoyaltyInterest" xlink:label="rytm_ThresholdAnnualNetRevenuesForRoyaltyInterest" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="rytm_ThresholdAnnualNetRevenuesForRoyaltyInterest" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_ThresholdPercentOfCumulativeMinimumPaymentsFundingToInvestors" xlink:label="rytm_ThresholdPercentOfCumulativeMinimumPaymentsFundingToInvestors" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="rytm_ThresholdPercentOfCumulativeMinimumPaymentsFundingToInvestors" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RepaymentsOfLongTermDebt" xlink:label="us-gaap_RepaymentsOfLongTermDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_RepaymentsOfLongTermDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_RevenueInterestsPayableCapAsPercentOfInvestmentAmount" xlink:label="rytm_RevenueInterestsPayableCapAsPercentOfInvestmentAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="rytm_RevenueInterestsPayableCapAsPercentOfInvestmentAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_RevenueInterestPaymentPeriodFromInitialClosing" xlink:label="rytm_RevenueInterestPaymentPeriodFromInitialClosing" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="rytm_RevenueInterestPaymentPeriodFromInitialClosing" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmbeddedDerivativeFairValueOfEmbeddedDerivativeLiability" xlink:label="us-gaap_EmbeddedDerivativeFairValueOfEmbeddedDerivativeLiability" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_EmbeddedDerivativeFairValueOfEmbeddedDerivativeLiability" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmbeddedDerivativeGainLossOnEmbeddedDerivativeNet" xlink:label="us-gaap_EmbeddedDerivativeGainLossOnEmbeddedDerivativeNet" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_EmbeddedDerivativeGainLossOnEmbeddedDerivativeNet" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DeferredRevenueNoncurrent" xlink:label="us-gaap_DeferredRevenueNoncurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DeferredRevenueNoncurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="rytm-20230930.xsd#rytm_ProceedsFromRoyaltyFinancingAgreement" xlink:label="rytm_ProceedsFromRoyaltyFinancingAgreement" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="rytm_ProceedsFromRoyaltyFinancingAgreement" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="13" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentInterestRateEffectivePercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DeferredFinanceCostsNet" xlink:label="us-gaap_DeferredFinanceCostsNet" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="14" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DeferredFinanceCostsNet" priority="1" use="optional" />
  </definitionLink>
</link:linkbase>
