Background/Aims: No standard chemotherapy has been established for advanced gallbladder cancer. The authors studied the activity and tolerability of a gemcitabine and ox-aliplatin (GEMOX) combination in unresectable gallbladder cancer (GBC). Methods: Adult patients with pathologically confirmed unresectable GBC were prospectively recruited at three centers. No patient had received prior chemotherapy or radiotherapy. Patients received cycles of gemcitabine at 1,000 mg/m2 on day 1, followed by oxaliplatin at 100 mg/m2 on day 2, every 2 weeks. The primary study endpoint was time to progression. Results: Forty patients with unresect-able GBC were enrolled. The median age was 60 years (range, 38 to 79 years). All patients showed good performance status. Of the 33 analyzable patients, 12 achieved partial re-sponse (36%), 17 stable disease (52%), and four progressive disease (12%). No patient achieved a complete response. The tumor control rate was 88%. At a median follow-up of 6.8 months, the median time to progression was 5.3 months (95% confidence interval [CI], 3.7 to 6.9), and median overall survival was 6.8 months (95% CI, 6.1 to 7.5). Nine of the 40 patients (23%) experienced at least a grade-3 adverse event, but no patient experienced a grade-4 adverse event. Conclu-sions: GEMOX combination therapy is a feasible option and is well tolerated in unresectable GBC. (Gut Liver 2013;7:594-598)