<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2023 Workiva-->
<!--r:48c599f6-2b2f-4980-953b-2f8c66af5f40,g:fe8e681b-5a79-4d49-9f95-00667daf7904-->
<xs:schema xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:lgnd="http://www.ligand.com/20230930" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:dtr-types1="http://www.xbrl.org/dtr/type/2020-01-21" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2022-03-31" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" attributeFormDefault="unqualified" elementFormDefault="qualified" targetNamespace="http://www.ligand.com/20230930">
  <xs:import namespace="http://fasb.org/srt/2023" schemaLocation="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd"/>
  <xs:import namespace="http://fasb.org/us-gaap/2023" schemaLocation="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd"/>
  <xs:import namespace="http://www.w3.org/1999/xlink" schemaLocation="http://www.xbrl.org/2003/xlink-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/linkbase" schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/2020-01-21" schemaLocation="https://www.xbrl.org/dtr/type/2020-01-21/types.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/2022-03-31" schemaLocation="https://www.xbrl.org/dtr/type/2022-03-31/types.xsd"/>
  <xs:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/dei/2023" schemaLocation="https://xbrl.sec.gov/dei/2023/dei-2023.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/ecd/2023" schemaLocation="https://xbrl.sec.gov/ecd/2023/ecd-2023.xsd"/>
  <xs:annotation>
    <xs:appinfo>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="lgnd-20230930_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="lgnd-20230930_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="lgnd-20230930_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="lgnd-20230930_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:type="simple"/>
      <link:roleType id="Cover" roleURI="http://www.ligand.com/role/Cover">
        <link:definition>0000001 - Document - Cover</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDBALANCESHEETS" roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDBALANCESHEETS">
        <link:definition>0000002 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDBALANCESHEETSParenthetical" roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDBALANCESHEETSParenthetical">
        <link:definition>0000003 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONS" roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONS">
        <link:definition>0000004 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDSTATEMENTSOFCOMPREHENSIVEINCOMELOSS" roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCOMPREHENSIVEINCOMELOSS">
        <link:definition>0000005 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY" roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY">
        <link:definition>0000006 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDSTATEMENTSOFCASHFLOWS" roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCASHFLOWS">
        <link:definition>0000007 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPolicies" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPolicies">
        <link:definition>0000008 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SaleofPelicanBusinessandInvestmentinPrimroseBio" roleURI="http://www.ligand.com/role/SaleofPelicanBusinessandInvestmentinPrimroseBio">
        <link:definition>0000009 - Disclosure - Sale of Pelican Business and Investment in Primrose Bio</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Acquisition" roleURI="http://www.ligand.com/role/Acquisition">
        <link:definition>0000010 - Disclosure - Acquisition</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SpinoffofOmniAb" roleURI="http://www.ligand.com/role/SpinoffofOmniAb">
        <link:definition>0000011 - Disclosure - Spin-off of OmniAb</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurements" roleURI="http://www.ligand.com/role/FairValueMeasurements">
        <link:definition>0000012 - Disclosure - Fair Value Measurements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Debt" roleURI="http://www.ligand.com/role/Debt">
        <link:definition>0000013 - Disclosure - Debt</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTax" roleURI="http://www.ligand.com/role/IncomeTax">
        <link:definition>0000014 - Disclosure - Income Tax</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockholdersEquity" roleURI="http://www.ligand.com/role/StockholdersEquity">
        <link:definition>0000015 - Disclosure - Stockholders' Equity</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentandContingencies" roleURI="http://www.ligand.com/role/CommitmentandContingencies">
        <link:definition>0000016 - Disclosure - Commitment and Contingencies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SubsequentEvents" roleURI="http://www.ligand.com/role/SubsequentEvents">
        <link:definition>0000017 - Disclosure - Subsequent Events</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesPolicies" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesPolicies">
        <link:definition>9954471 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesTables" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesTables">
        <link:definition>9954472 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SaleofPelicanBusinessandInvestmentinPrimroseBioTables" roleURI="http://www.ligand.com/role/SaleofPelicanBusinessandInvestmentinPrimroseBioTables">
        <link:definition>9954473 - Disclosure - Sale of Pelican Business and Investment in Primrose Bio (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AcquisitionTables" roleURI="http://www.ligand.com/role/AcquisitionTables">
        <link:definition>9954474 - Disclosure - Acquisition (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SpinoffofOmniAbTables" roleURI="http://www.ligand.com/role/SpinoffofOmniAbTables">
        <link:definition>9954475 - Disclosure - Spin-off of OmniAb (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurementsTables" roleURI="http://www.ligand.com/role/FairValueMeasurementsTables">
        <link:definition>9954476 - Disclosure - Fair Value Measurements (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockholdersEquityTables" roleURI="http://www.ligand.com/role/StockholdersEquityTables">
        <link:definition>9954477 - Disclosure - Stockholders' Equity (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesNarrativeDetails" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesNarrativeDetails">
        <link:definition>9954478 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesRevenuebySourceDetails" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesRevenuebySourceDetails">
        <link:definition>9954479 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies - Revenue by Source (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesInvestmentCategoriesDetails" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesInvestmentCategoriesDetails">
        <link:definition>9954480 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies - Investment Categories (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesAvailableforSaleDebtSecuritiesbyContractualMaturityDetails" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesAvailableforSaleDebtSecuritiesbyContractualMaturityDetails">
        <link:definition>9954481 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies - Available-for-Sale Debt Securities by Contractual Maturity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesGoodwillandOtherIdentifiableIntangibleAssetsDetails" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesGoodwillandOtherIdentifiableIntangibleAssetsDetails">
        <link:definition>9954482 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies - Goodwill and Other Identifiable Intangible Assets (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesCommercialLicenseRightsDetails" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesCommercialLicenseRightsDetails">
        <link:definition>9954483 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies - Commercial License Rights (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesAccruedLiabilitiesandOtherLongTermLiabilitiesDetails" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesAccruedLiabilitiesandOtherLongTermLiabilitiesDetails">
        <link:definition>9954484 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies - Accrued Liabilities and Other Long-Term Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesAccountingforShareBasedCompensationDetails" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesAccountingforShareBasedCompensationDetails">
        <link:definition>9954485 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies - Accounting for Share-Based Compensation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesFairValueValuationAssumptionsDetails" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesFairValueValuationAssumptionsDetails">
        <link:definition>9954486 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies - Fair Value Valuation Assumptions (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BasisofPresentationandSummaryofSignificantAccountingPoliciesEarningsLossPerShareDetails" roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesEarningsLossPerShareDetails">
        <link:definition>9954487 - Disclosure - Basis of Presentation and Summary of Significant Accounting Policies - Earnings (Loss) Per Share (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SaleofPelicanBusinessandInvestmentinPrimroseBioNarrativeDetails" roleURI="http://www.ligand.com/role/SaleofPelicanBusinessandInvestmentinPrimroseBioNarrativeDetails">
        <link:definition>9954488 - Disclosure - Sale of Pelican Business and Investment in Primrose Bio - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SaleofPelicanBusinessandInvestmentinPrimroseBioNetAssetDetails" roleURI="http://www.ligand.com/role/SaleofPelicanBusinessandInvestmentinPrimroseBioNetAssetDetails">
        <link:definition>9954489 - Disclosure - Sale of Pelican Business and Investment in Primrose Bio - Net Asset (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SaleofPelicanBusinessandInvestmentinPrimroseBioFairValueoftheConsiderationDetails" roleURI="http://www.ligand.com/role/SaleofPelicanBusinessandInvestmentinPrimroseBioFairValueoftheConsiderationDetails">
        <link:definition>9954490 - Disclosure - Sale of Pelican Business and Investment in Primrose Bio - Fair Value of the Consideration (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AcquisitionNarrativeDetails" roleURI="http://www.ligand.com/role/AcquisitionNarrativeDetails">
        <link:definition>9954491 - Disclosure - Acquisition - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AcquisitionAssetsAcquiredandLiabilitiesAssumedDetails" roleURI="http://www.ligand.com/role/AcquisitionAssetsAcquiredandLiabilitiesAssumedDetails">
        <link:definition>9954492 - Disclosure - Acquisition - Assets Acquired and Liabilities Assumed (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SpinoffofOmniAbNarrativeDetails" roleURI="http://www.ligand.com/role/SpinoffofOmniAbNarrativeDetails">
        <link:definition>9954493 - Disclosure - Spin-off of OmniAb - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SpinoffofOmniAbScheduleofrevenueandexpensesofthediscontinuedoperationsDetails" roleURI="http://www.ligand.com/role/SpinoffofOmniAbScheduleofrevenueandexpensesofthediscontinuedoperationsDetails">
        <link:definition>9954494 - Disclosure - Spin-off of OmniAb - Schedule of revenue and expenses of the discontinued operations (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SpinoffofOmniAbScheduleofnoncashitemsandcapitalexpendituresofthediscontinuedoperationsDetails" roleURI="http://www.ligand.com/role/SpinoffofOmniAbScheduleofnoncashitemsandcapitalexpendituresofthediscontinuedoperationsDetails">
        <link:definition>9954495 - Disclosure - Spin-off of OmniAb - Schedule of non-cash items and capital expenditures of the discontinued operations (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurementsAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails" roleURI="http://www.ligand.com/role/FairValueMeasurementsAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails">
        <link:definition>9954496 - Disclosure - Fair Value Measurements - Assets and Liabilities Measured at Fair Value on Recurring Basis (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurementsReconciliationofLevel3FinancialInstrumentsDetails" roleURI="http://www.ligand.com/role/FairValueMeasurementsReconciliationofLevel3FinancialInstrumentsDetails">
        <link:definition>9954497 - Disclosure - Fair Value Measurements - Reconciliation of Level 3 Financial Instruments (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurementsNarrativeDetails" roleURI="http://www.ligand.com/role/FairValueMeasurementsNarrativeDetails">
        <link:definition>9954498 - Disclosure - Fair Value Measurements - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="DebtNarrativeDetails" roleURI="http://www.ligand.com/role/DebtNarrativeDetails">
        <link:definition>9954499 - Disclosure - Debt - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxDetails" roleURI="http://www.ligand.com/role/IncomeTaxDetails">
        <link:definition>9954500 - Disclosure - Income Tax (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockholdersEquityStockOptionPlanandRestrictedStockActivityDetails" roleURI="http://www.ligand.com/role/StockholdersEquityStockOptionPlanandRestrictedStockActivityDetails">
        <link:definition>9954501 - Disclosure - Stockholders' Equity - Stock Option Plan and Restricted Stock Activity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockholdersEquityNarrativeDetails" roleURI="http://www.ligand.com/role/StockholdersEquityNarrativeDetails">
        <link:definition>9954502 - Disclosure - Stockholders' Equity - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentandContingenciesNarrativeDetails" roleURI="http://www.ligand.com/role/CommitmentandContingenciesNarrativeDetails">
        <link:definition>9954503 - Disclosure - Commitment and Contingencies - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SubsequentEventsDetails" roleURI="http://www.ligand.com/role/SubsequentEventsDetails">
        <link:definition>9954504 - Disclosure - Subsequent Events (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </xs:appinfo>
  </xs:annotation>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationNetContributions" abstract="false" name="DisposalGroupIncludingDiscontinuedOperationNetContributions" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_DeferredTaxAssetsAdjustments" abstract="false" name="DeferredTaxAssetsAdjustments" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_BusinessCombinationNumberOfContingentValueRightsIssuedPerAcquireeShare" abstract="false" name="BusinessCombinationNumberOfContingentValueRightsIssuedPerAcquireeShare" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="lgnd_AccruedCustomerDepositsCurrent" abstract="false" name="AccruedCustomerDepositsCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_KyprolisMember" abstract="true" name="KyprolisMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_BasisOfPresentationLineItems" abstract="true" name="BasisOfPresentationLineItems" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_CostAllocationDomain" abstract="true" name="CostAllocationDomain" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_SalesRevenueMilestone" abstract="false" name="SalesRevenueMilestone" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_AdjustmentsToAdditionalPaidInCapitalWarrantAndBondHedgeUnwindTransactions" abstract="false" name="AdjustmentsToAdditionalPaidInCapitalWarrantAndBondHedgeUnwindTransactions" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_NovanIncMember" abstract="true" name="NovanIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_PelicanTechnologyHoldingsIncMember" abstract="true" name="PelicanTechnologyHoldingsIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_EquitySecuritiesCostsMember" abstract="true" name="EquitySecuritiesCostsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_CurrentAndExpectedCreditLossAdjustment" abstract="false" name="CurrentAndExpectedCreditLossAdjustment" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_SelexisAndDianomiMember" abstract="true" name="SelexisAndDianomiMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_AtTheMarketEquityOfferingMember" abstract="true" name="AtTheMarketEquityOfferingMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_ProceedsFromCommercialLicenseRights" abstract="false" name="ProceedsFromCommercialLicenseRights" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_BusinessCombinationNumberOfContingentValueRightsIssuedFromEachContingentValueRightSeries" abstract="false" name="BusinessCombinationNumberOfContingentValueRightsIssuedFromEachContingentValueRightSeries" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="lgnd_BusinessCombinationFrequencyOfCashPaymentsToContingentValueRightsHolders" abstract="false" name="BusinessCombinationFrequencyOfCashPaymentsToContingentValueRightsHolders" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="lgnd_InterestInPotentialDevelopmentMilestone" abstract="false" name="InterestInPotentialDevelopmentMilestone" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lgnd_BelowMilestoneMember" abstract="true" name="BelowMilestoneMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationShareBasedPaymentArrangementExpense" abstract="false" name="DisposalGroupIncludingDiscontinuedOperationShareBasedPaymentArrangementExpense" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_EquitySecuritiesAllocationMember" abstract="true" name="EquitySecuritiesAllocationMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherLiabilities" abstract="false" name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherLiabilities" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_EmployeeStockPurchasePlanAbstract" abstract="true" name="EmployeeStockPurchasePlanAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_PrimordialGeneticsMember" abstract="true" name="PrimordialGeneticsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_Phase3ClinicalTrialMember" abstract="true" name="Phase3ClinicalTrialMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationFinancingLeaseRightOfUseAsset" abstract="false" name="DisposalGroupIncludingDiscontinuedOperationFinancingLeaseRightOfUseAsset" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_LiabilityForContingentValueRights" abstract="false" name="LiabilityForContingentValueRights" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_NucorionMember" abstract="true" name="NucorionMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_SecuredOvernightFinancingRateSOFRMember" abstract="true" name="SecuredOvernightFinancingRateSOFRMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationFinancingActivitiesAbstract" abstract="true" name="DisposalGroupIncludingDiscontinuedOperationFinancingActivitiesAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_ConsiderationClassficationAxis" abstract="true" name="ConsiderationClassficationAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_DerivativeAssetsMember" abstract="true" name="DerivativeAssetsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_ScheduleOfFairValueOfTheConsiderationTableTextBlock" abstract="false" name="ScheduleOfFairValueOfTheConsiderationTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="lgnd_RylazeMember" abstract="true" name="RylazeMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_NumberOfContracts" abstract="false" name="NumberOfContracts" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="lgnd_MaterialSalesCaptisolMember" abstract="true" name="MaterialSalesCaptisolMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_ToleranceTherapeuticsMember" abstract="true" name="ToleranceTherapeuticsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_PeliCRM197Member" abstract="true" name="PeliCRM197Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_AboveMilestoneMember" abstract="true" name="AboveMilestoneMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_PrimroseBioMember" abstract="true" name="PrimroseBioMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_ContingentMilestonePurchaseAgreement" abstract="false" name="ContingentMilestonePurchaseAgreement" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_AmortizationOfCommercialLicenseAndOtherEconomicRights" abstract="false" name="AmortizationOfCommercialLicenseAndOtherEconomicRights" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationShareConsideration" abstract="false" name="DisposalGroupIncludingDiscontinuedOperationShareConsideration" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="lgnd_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedTangibleAssetsAcquiredNetOfCashAndRestrictedCashReceived" abstract="false" name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedTangibleAssetsAcquiredNetOfCashAndRestrictedCashReceived" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_NetCashProvidedByUsedInDiscontinuedOperationsInvestingActivitiesAbstract" abstract="true" name="NetCashProvidedByUsedInDiscontinuedOperationsInvestingActivitiesAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_EvomelaMember" abstract="true" name="EvomelaMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_AdjustmentsToAdditionalPaidInCapitalTaxReturnToProvision" abstract="false" name="AdjustmentsToAdditionalPaidInCapitalTaxReturnToProvision" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_BrowseTaxonomyDisposalGroupIncludingDiscontinuedOperationOtherIncomeExpenseAbstract" abstract="true" name="BrowseTaxonomyDisposalGroupIncludingDiscontinuedOperationOtherIncomeExpenseAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_BasisOfPresentationTable" abstract="true" name="BasisOfPresentationTable" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_PaymentsForConvertibleBondHedges" abstract="false" name="PaymentsForConvertibleBondHedges" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_SaleOfStockAuthorizedOfferingAmount" abstract="false" name="SaleOfStockAuthorizedOfferingAmount" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_FinanceLeaseAndOperatingLeaseRightOfUseAssetAmortization" abstract="false" name="FinanceLeaseAndOperatingLeaseRightOfUseAssetAmortization" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_NumberOfContingentValueRightsSeries" abstract="false" name="NumberOfContingentValueRightsSeries" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="lgnd_OmniAbMember" abstract="true" name="OmniAbMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationPercentageOfVotingInterestsDisposed" abstract="false" name="DisposalGroupIncludingDiscontinuedOperationPercentageOfVotingInterestsDisposed" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationOperatingCostsAndExpensesAbstract" abstract="true" name="DisposalGroupIncludingDiscontinuedOperationOperatingCostsAndExpensesAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_AmountsOwedToFormerLicensorFairValueDisclosure" abstract="false" name="AmountsOwedToFormerLicensorFairValueDisclosure" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_AccruedSubcontractorExpensesCurrent" abstract="false" name="AccruedSubcontractorExpensesCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_LicenseFeesMilestonesAndProductOtherProductOtherMember" abstract="true" name="LicenseFeesMilestonesAndProductOtherProductOtherMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_COVID19AccountsReceivableAllowanceForCreditLossPeriodIncreaseDecrease" abstract="false" name="COVID19AccountsReceivableAllowanceForCreditLossPeriodIncreaseDecrease" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_LicenseeAccrualCurrent" abstract="false" name="LicenseeAccrualCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationLongTermOperatingLeaseLiabilities" abstract="false" name="DisposalGroupIncludingDiscontinuedOperationLongTermOperatingLeaseLiabilities" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_PaymentsToContingentValueRightHolders" abstract="false" name="PaymentsToContingentValueRightHolders" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_CostAllocationAxis" abstract="true" name="CostAllocationAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_EquityMethodInvestmentCostsMember" abstract="true" name="EquityMethodInvestmentCostsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLeaseLiabilities" abstract="false" name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLeaseLiabilities" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_BusinessSpinOffAndMigrationPolicyTextBlock" abstract="false" name="BusinessSpinOffAndMigrationPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationNetAsset" abstract="false" name="DisposalGroupIncludingDiscontinuedOperationNetAsset" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_AccruedInventoryPurchases" abstract="false" name="AccruedInventoryPurchases" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_NetCashProvidedByUsedInDiscontinuedOperationsOperatingActivitiesAbstract" abstract="true" name="NetCashProvidedByUsedInDiscontinuedOperationsOperatingActivitiesAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_MilestoneMember" abstract="true" name="MilestoneMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationChangeInAmountOfContingentConsideration" abstract="false" name="DisposalGroupIncludingDiscontinuedOperationChangeInAmountOfContingentConsideration" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_OtherLongTermAssetsCostsMember" abstract="true" name="OtherLongTermAssetsCostsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationResearchAndDevelopment" abstract="false" name="DisposalGroupIncludingDiscontinuedOperationResearchAndDevelopment" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_BusinessCombinationContingentConsiderationLiabilityFairValueDisclosure" abstract="false" name="BusinessCombinationContingentConsiderationLiabilityFairValueDisclosure" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_LesseeIncreaseDecreaseInOperatingLeaseAssetsDueToModification" abstract="false" name="LesseeIncreaseDecreaseInOperatingLeaseAssetsDueToModification" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_RoyaltyOtherMember" abstract="true" name="RoyaltyOtherMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_ContractRevenueMember" abstract="true" name="ContractRevenueMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_ScheduleOfShortTermInvestmentsTableTextBlock" abstract="false" name="ScheduleOfShortTermInvestmentsTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="lgnd_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI" abstract="false" name="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFVNI" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_ScheduleOfCommercialLicenseRightsTableTextBlock" abstract="false" name="ScheduleOfCommercialLicenseRightsTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="lgnd_EquityMethodInvestmentsAllocationMember" abstract="true" name="EquityMethodInvestmentsAllocationMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationOperatingLeaseRightOfUseAsset" abstract="false" name="DisposalGroupIncludingDiscontinuedOperationOperatingLeaseRightOfUseAsset" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_OvidTherapeuticsMember" abstract="true" name="OvidTherapeuticsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_ScheduleForShareBasedCompensationExpenseForAwardsToEmployeesAndDirectorsTableTextBlock" abstract="false" name="ScheduleForShareBasedCompensationExpenseForAwardsToEmployeesAndDirectorsTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="lgnd_AccruedSupplierExpensesCurrent" abstract="false" name="AccruedSupplierExpensesCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedRightOfUseAssets" abstract="false" name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedRightOfUseAssets" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_TeriparatideInjectionMember" abstract="true" name="TeriparatideInjectionMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherAssets" abstract="false" name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherAssets" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_ConvertibleSeniorNotesDue2023Member" abstract="true" name="ConvertibleSeniorNotesDue2023Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_PaymentsToContingentValueRightHoldersInvestingActivity" abstract="false" name="PaymentsToContingentValueRightHoldersInvestingActivity" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_SoticlestatMember" abstract="true" name="SoticlestatMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_NonCashChangeInEstimatedFairValueOfContingentValueRights" abstract="false" name="NonCashChangeInEstimatedFairValueOfContingentValueRights" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_NotesRepurchasedDuringCurrentPeriodTwoMember" abstract="true" name="NotesRepurchasedDuringCurrentPeriodTwoMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_AdjustmentsToAdditionalPaidInCapitalIncreaseDueToSeparation" abstract="false" name="AdjustmentsToAdditionalPaidInCapitalIncreaseDueToSeparation" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_BusinessCombinationAcquisitionCostIncurredButNotYetPaid" abstract="false" name="BusinessCombinationAcquisitionCostIncurredButNotYetPaid" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_CommercialLicenseRights" abstract="false" name="CommercialLicenseRights" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_ConsiderationPaidForAnInterestInPotentialDevelopmentMilestone" abstract="false" name="ConsiderationPaidForAnInterestInPotentialDevelopmentMilestone" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_MilestoneDomain" abstract="true" name="MilestoneDomain" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_CommercialLicenseAndOtherEconomicRightsAbstract" abstract="true" name="CommercialLicenseAndOtherEconomicRightsAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_EquitySecuritiesFVNIShareSoldInPeriod" abstract="false" name="EquitySecuritiesFVNIShareSoldInPeriod" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="lgnd_MaterialSalesCaptisolCoreMember" abstract="true" name="MaterialSalesCaptisolCoreMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_ContingentLiabilitiesMember" abstract="true" name="ContingentLiabilitiesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_USDistrictCourtForTheNorthernDistrictOfOhioMember" abstract="true" name="USDistrictCourtForTheNorthernDistrictOfOhioMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_PaymentsToContingentValueRightHoldersFinancingActivity" abstract="false" name="PaymentsToContingentValueRightHoldersFinancingActivity" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_CyDexMember" abstract="true" name="CyDexMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_DebtInstrumentRepurchasedAmountDuringPeriod" abstract="false" name="DebtInstrumentRepurchasedAmountDuringPeriod" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_PaymentsToUnwindWarrants" abstract="false" name="PaymentsToUnwindWarrants" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_FiniteLivedIntangibleAssetAccumulatedImpairment" abstract="false" name="FiniteLivedIntangibleAssetAccumulatedImpairment" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_BusinessCombinationAcquiredPercentage" abstract="false" name="BusinessCombinationAcquiredPercentage" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lgnd_ShareBasedCompensationAchievementOfPerformanceCriteriaPayoutRangePercent" abstract="false" name="ShareBasedCompensationAchievementOfPerformanceCriteriaPayoutRangePercent" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:percentItemType"/>
  <xs:element id="lgnd_FiniteLivedIntangibleAssetsAccumulatedAmortizationCreditLossAdjustments" abstract="false" name="FiniteLivedIntangibleAssetsAccumulatedAmortizationCreditLossAdjustments" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_SalesContractInterestInSalesRevenue" abstract="false" name="SalesContractInterestInSalesRevenue" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lgnd_ElutiaMember" abstract="true" name="ElutiaMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_ElutiaAndCorMatrixMember" abstract="true" name="ElutiaAndCorMatrixMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_ConsiderationClassficationDomain" abstract="true" name="ConsiderationClassficationDomain" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lgnd_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsDiscountRate" abstract="false" name="BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsDiscountRate" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:percentItemType"/>
  <xs:element id="lgnd_MaterialSalesCaptisolCOVIDMember" abstract="true" name="MaterialSalesCaptisolCOVIDMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_DisposalGroupIncludingDiscontinuedOperationsCapitalExpendituresIncurredButNotYetPaid" abstract="false" name="DisposalGroupIncludingDiscontinuedOperationsCapitalExpendituresIncurredButNotYetPaid" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_GainLossOnShortTermInvestments" abstract="false" name="GainLossOnShortTermInvestments" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_EmployeeStockPurchasePlanMember" abstract="true" name="EmployeeStockPurchasePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_MilestoneAxis" abstract="true" name="MilestoneAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="lgnd_FiniteLivedIntangibleAssetsCreditLossAdjustments" abstract="false" name="FiniteLivedIntangibleAssetsCreditLossAdjustments" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_CommercialLicenseRightsPolicyTextBlock" abstract="false" name="CommercialLicenseRightsPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="lgnd_BusinessCombinationLoanFeesAndInterest" abstract="false" name="BusinessCombinationLoanFeesAndInterest" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lgnd_DevelopmentRegulatoryCommercialMilestonesAndTieredRoyaltiesMember" abstract="true" name="DevelopmentRegulatoryCommercialMilestonesAndTieredRoyaltiesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="lgnd_MetabasisMember" abstract="true" name="MetabasisMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
</xs:schema>
