Background: Biliary tract cancers (BTCs) include cholangiocarcinoma, which refers to cancers arising in the intrahepatic, perihilar or distal biliary tree, ampulla of vater and gallbladder carcinoma. Even after complete surgical resection, a large number of BTC patients develop recurrence. Whether recurrence after surgery and de novo metastatic BTC should have comparable stratification in first-line palliative systemic therapy clinical studies is unknown. Methods: 480 patients who received palliative chemotherapy as first-line treatment for advanced BTC between January 1987 and May 2014 in Princess Margaret Cancer Centre, Toronto were reviewed. Probability of overall survival (OS) was estimated using the Kaplan-Meier method, and independent prognostic factors for OS were identified using the multivariable Cox proportional hazard model. Results: There were 171 recurrent and 309 de novo metastatic patients. Median age at diagnosis was 62 years, performance status<2; 436 (91%) patients, male; 262 (55%). In the recurrent group, 91 (53%) had indwelling stents, ampulla of vater; 50 (29%), gallbladder; 29 (17%), cholangiocarcinoma; 92 (54%). In the de novo metastatic group, 185 (60%) had indwelling stents, primary site was ampulla of vater; 16 (5%), gallbladder; 94 (30%), cholangiocarcinoma; 199 (65%). Systemic treatment received was gemcitabine/platinum doublet in 134 (28%), gemcitabine/5-FU doublet; 186 (39%), gemcitabine; 97 (20%), other; 63 (20%). Median OS for the recurrent group who received first-line palliative chemotherapy was 15.6 months (95% confidence interval [CI] 13.5-18.0) and 14.4 months (95% CI 12.0-16.0) in the de novo metastatic group. Multivariable analysis for OS revealed that gallbladder as the primary site (P=0.03) and ECOG performance status ≥2 (P=0.001) were prognostic for worse OS. De novo metastatic status was not prognostic for worse OS compared with recurrent status (Hazard ratio 1.1, 95% CI 0.82-1.50, P=0.51). Conclusions: Similar treatment of patients with recurrent disease after surgery and de novo metastatic BTC, with first-line palliative chemotherapy is acceptable.