Background: The results of ABC-2 trial established gemcitabine and cisplatin (gem-cis) as a standard regimen for advanced biliary cancer. Although no randomized trial has been performed with gemcitabine and capecitabine (gem-cap), this regimen has reported benefits and has been a standard treatment at our institution. We report our experience with outcomes and toxicity. Methods: This is a single institution, retrospective study from 2005-2015 of patients with advanced biliary cancer, including intra and extrahepatic cholangiocarcinoma (IHCC/EHCC) and gallbladder carcinoma (GBC). Overall survival (OS) and progression-free survival (PFS) on gem-cap were reported using standard Kaplan-Meier methods. Comparisons were made using log-rank test. Results: A total of 372 patients were identified. Of these, 227 (61.0%) had chemotherapy data at our institution. A total of 153 patients (41.1%) received gem-cap, 133/153 (86.9%) received it in first line. The majority of patients (67.4%) had metastatic disease. Twenty-seven patients (17.6%) received it as adjuvant therapy, of which 16 (10.5%) also received adjuvant radiation. Forty-four patients (33.1%) received second line of chemotherapy and 12 (9.0%) received third line. Disease sites included 48.9% IHCC, 24.0% EHCC and 27.1% GBC. Median follow-up was 45.1 months (mo). The median OS and PFS for the entire cohort were 13.0 mo (95% CI 10.7-17.4) and 8.0 mo (6.0-9.3), respectively. Patients with metastatic disease had poorer OS and PFS compared to locally advanced disease: median OS – 11.4 vs 16.3 mo (p = 0.01); median PFS – 6.9 vs 10.4 mo (p < 0.001). There was no statistically significant differences in OS/PFS by disease site. Overall, 69 patients (55.6%) experienced grade 3/4 toxicity. The most common (35.7%) was hematologic toxicity (neutropenia/thrombocytopenia). Other adverse events included elevated LFT’s (9.3%) and non-hematologic events (22.5%), including fatigue (6.8%) and hand-foot syndrome (6.0%). Conclusions: Gem-cap provides a similar PFS to gem-cis based on historical comparison with ABC-2 trial. Gem-cap may offer the advantage of fewer adverse events (55.6%) compared to the 70.7% reported in ABC-2. Prospective comparison of these two regimens is warranted.