Background: BTC is a heterogeneous group of disease consisted of intrahepatic, extrahepatic cholangiocarcinoma and gallbladder cancer. Although GEMCIS has been established as a standard first-line chemotherapy based on the ABC-02 trial, more data is needed to define the clinical course of BTC and its prognostic factors. Methods: Between April 2010 and May 2015, 740 pts with histologically documented BTC were treated with first-line GEMCIS in Asan Medical Center, Seoul, Korea. All pts received GEMCIS as described in the ABC-02 trial. Response was graded according to the RECIST version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Maier curves. Multivariate analyses were performed to define prognostic factors. Results: Median age was 60 years (range, 27-82) and 425 (57%) pts were male. Initially metastatic disease was the most common disease status at GEMCIS (n = 377, 51%) followed by recurrence after surgery (279, 38%) and locally advanced unresectable disease (84, 11%). Liver (37%) and peritoneum (25%) were the common metastatic sites. Pts received a median 5 cycles of GEMCIS (range, 1-42). Objective response rates were 13% and there was no significant difference according to the primary tumor sites (p = 0.45). With a median follow-up duration of 27.3 months (mo) (95% CI, 24.2-30.5), median PFS and OS were 5.2 mo (95% CI, 4.7-5.6) and 10.4 mo (95% CI, 9.6-11.2), respectively. In the multivariate analyses, male gender (female vs male; HR = 0.83), pretreatment CA 19-9 level (elevated vs normal; HR = 1.31), initially metastatic disease (vs locally advanced disease, HR = 1.92), poor performance status (ECOG 2 vs 0-1; HR = 1.45), and measurable disease by the RECIST criteria (vs non-measurable; HR = 1.40) were significantly associated with poorer OS (p < 0.05 for all). Conclusions: Our retrospective analysis based on large number of pts demonstrated that first-line GEMCIS in the real world setting has comparable efficacy with the results of the ABC-02 trial. Prognostic factors demonstrated in this study may help to predict clinical outcomes and design future clinical trials for advanced BTC.