Purpose: The BILCAP study described a modest benefit for capecitabine as adjuvant therapy for curatively resected biliary tract cancer (BTC), and capecitabine has become the standard of care. We present the long-term data and novel exploratory subgroup analyses., Methods: This randomized, controlled, multicenter, phase III study recruited patients age 18 years or older with histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer after resection with curative intent and an Eastern Cooperative Oncology Group performance status of < 2. Patients were randomly assigned 1:1 to receive oral capecitabine (1,250 mg/m 2 twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation. The primary outcome was overall survival (OS). This study is registered with EudraCT 2005-003318-13., Results: Between March 15, 2006, and December 4, 2014, 447 patients were enrolled; 223 patients with BTC resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. At the data cutoff of January 21, 2021, the median follow-up for all patients was 106 months (95% CI, 98 to 108). In the intention-to-treat analysis, the median OS was 49.6 months (95% CI, 35.1 to 59.1) in the capecitabine group compared with 36.1 months (95% CI, 29.7 to 44.2) in the observation group (adjusted hazard ratio 0.84; 95% CI, 0.67 to 1.06). In a protocol-specified sensitivity analysis, adjusting for minimization factors, nodal status, grade, and sex, the OS hazard ratio was 0.74 (95% CI, 0.59 to 0.94). We further describe the prognostic impact of R status, grade, nodal status, and sex., Conclusion: This long-term analysis supports the previous analysis, suggesting that capecitabine can improve OS in patients with resected BTC when used as adjuvant chemotherapy after surgery and should be considered as the standard of care., Competing Interests: John BridgewaterHonoraria: Merck Serono, ServierConsulting or Advisory Role: Merck Serono, Servier, Roche, Bayer, AstraZeneca, Incyte, Basilea, Taiho OncologySpeakers' Bureau: Celgene, Amgen, Bristol Myers SquibbResearch Funding: Amgen, Incyte (Inst)Travel, Accommodations, Expenses: MSD Oncology, Merck Serono, Servier, Bristol Myers Squibb/Medarex, Bristol Myers Squibb Daniel H. PalmerConsulting or Advisory Role: BMS (Inst), MSD, AstraZeneca, Eisai, Sirtex Medical, Roche, Boston Scientific, ViatrisResearch Funding: BMS, Bayer, Sirtex Medical, AstraZeneca, NuCana Darius MirzaStock and Other Ownership Interests: OrganOx Ltd Pippa CorrieHonoraria: Novartis, Merck Sharp & Dohme, Pierre Fabre, Bristol Myers SquibbConsulting or Advisory Role: Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Incyte, Pierre Fabre, Roche, MicrobioticaSpeakers' Bureau: Merck Sharp & Dohme, Novartis, Bristol Myers SquibbResearch Funding: MSD (Inst), Bristol Myers Squibb (Inst), Novartis (Inst), Array BioPharma (Inst), Celgene (Inst), Halozyme (Inst), Iovance Biotherapeutics (Inst), Lilly (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck Sharp & Dohme Stephen FalkStock and Other Ownership Interests: GlaxoSmithKlineConsulting or Advisory Role: BMSSpeakers' Bureau: Merck Serono, Servier, AmgenResearch Funding: Gilead Sciences (Inst), AstraZeneca (Inst), Novartis (Inst)Travel, Accommodations, Expenses: CelgeneOther Relationship: Servier Harpreet WasanHonoraria: Merck KGaA, Celgene, Sirtex Medical, Servier, Array BioPharma, Roche/Genentech, ERYTECH Pharma, Incyte, ZymeworksConsulting or Advisory Role: Roche Pharma AG, ERYTECH Pharma, Shire, Incyte, Sirtex medical, Pierre Fabre, Pfizer, BayerSpeakers' Bureau: Sirtex Medical, Celgene, Merck KGaA, Servier, IncyteResearch Funding: Sirtex Medical (Inst), Merck KGaA (Inst), Pfizer (Inst), Merck Sharp & Dohme (Inst) Paul RossStock and Other Ownership Interests: Perci HealthHonoraria: Sirtex Medical, Roche, AstraZeneca, MerckConsulting or Advisory Role: Sirtex Medical, Roche, AstraZeneca, Amgen, Boston ScientificSpeakers' Bureau: Amgen, Merck, Servier, Boston Scientific, Roche, EisaiResearch Funding: Sanofi (Inst), Bayer (Inst)Travel, Accommodations, Expenses: Roche, Ipsen Lucy WallResearch Funding: Merck Serono Jonathan WadsleyConsulting or Advisory Role: Lilly (Inst), Novartis (Inst), Roche (Inst), Ipsen (Inst), Bayer (Inst)Speakers' Bureau: Genzyme, EisaiResearch Funding: AstraZeneca, Genzyme Thomas R. EvansHonoraria: Eisai (Inst), Merck Sharp & Dohme (Inst), Bristol Myers Squibb (Inst), NuCana (Inst), Roche/Genentech (Inst), Ascelia (Inst), AstraZeneca (Inst), Bicycle Therapeutics (Inst), Medivir (Inst)Consulting or Advisory Role: Karus Therapeutics (Inst)Speakers' Bureau: Eisai (Inst), Bristol Myers Squibb (Inst), Merck Sharp & Dohme (Inst), NuCana (Inst), United Medical (Inst), AstraZeneca (Inst), Roche/Genentech (Inst), Medivir (Inst)Research Funding: Bristol Myers Squibb (Inst), AstraZeneca (Inst), BeiGene (Inst), Basilea (Inst), Celgene (Inst), Eisai (Inst), Merck Sharp & Dohme (Inst), MiNA Therapeutics (Inst), Bicycle Therapeutics (Inst), Lilly (Inst), Merck Serono (Inst), Janssen (Inst), Johnson & Johnson (Inst), Verastem (Inst), Roche/Genentech (Inst), Novartis (Inst), Iovance Biotherapeutics (Inst), Medivir (Inst), Sanofi/Aventis (Inst), Clovis Oncology (Inst), Plexxikon (Inst), NuCana (Inst), Sierra Pharma (Inst), GlaxoSmithKline (Inst), Halozyme (Inst), CytomX Therapeutics (Inst), Vertex (Inst), Athenex (Inst), Adaptimmune (Inst), Immunocore (Inst), Modulate Pharma (Inst), Berg Pharma (Inst), Starpharma (Inst), BiolineRx (Inst), iOnctura (Inst), UCB (Inst), Sapience Therapeutics (Inst), Astellas Pharma (Inst), Boehringer Ingelheim (Inst), Seattle Genetics (Inst)Expert Testimony: Medivir (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, Eisai, NuCanaOther Relationship: Genmab (Inst) Deborah StockenResearch Funding: Abbott Diabetes (Inst) Yuk Ting MaHonoraria: Boston ScientificConsulting or Advisory Role: Eisai, Roche, AstraZeneca/MedImmune, Ipsen, Faron PharmaceuticalsResearch Funding: Eisai (Inst), AstraZeneca/Merck (Inst), Faron Pharmaceuticals (Inst), MINA Therapeutics (Inst) John NeoptolemosResearch Funding: Dietmar Hopp Stiftung (Inst), Stiftung Deutsche Krebshilfe (Inst), Heidelberger Stiftung Chirurgie (Inst) Timothy IvesonHonoraria: Servier, AmgenConsulting or Advisory Role: Servier, Bristol Myers Squibb, Pierre Fabre, MSD Oncology David CunninghamStock and Other Ownership Interests: OVIBIOConsulting or Advisory Role: OVIBIOResearch Funding: Celgene (Inst), MedImmune (Inst), Bayer (Inst), 4SC (Inst), Clovis Oncology (Inst), Lilly (Inst), Roche (Inst), Leap Oncology (Inst) Juan W. ValleHonoraria: IpsenConsulting or Advisory Role: Ipsen, Novartis, AstraZeneca, Merck, Agios, Pfizer, PCI Biotech, Incyte, Keocyt, QED Therapeutics, Pieris Pharmaceuticals, Genoscience Pharma, Mundipharma EDO GmbH, Wren Laboratories, NuCana, SERVIER, Debiopharm Group, Imaging Equipment Limited, Hutchison MediPharma, Zymeworks, Aptitude Health, Sirtex Medical, Baxter, Medivir, Cantargia ABSpeakers' Bureau: Novartis, Ipsen, NuCana, Imaging Equipment Limited, Mylan, Incyte, ServierTravel, Accommodations, Expenses: NuCana, Lilly, Roche, AstraZeneca/MedImmuneNo other potential conflicts of interest were reported.