ABSTRACT: PURPOSE: Disease-specific survival (DSS) for proximal bile duct cancer has been reported to be worse than for carcinoma of the distal duct. METHODS: Review of two prospectively maintained databases identified 204 patients who underwent resection for extrahepatic cholangiocarcinoma (proximal: n=106, 52%; distal: n=98, 48%) between December 1987 and December 2005. Patient, tumor, and treatment-related variables were reviewed. Analyses were performed to compare tumor presentation, treatment, and DSS between patients with resected proximal and distal lesions. RESULTS: Median follow-up for the 204 resected patients was 24 months (range 1-165 months) and 56 months for those alive at last follow-up. Combined liver/bile duct resection was performed in 82% of patients with proximal lesions, and pancreaticoduodenectomy was performed in 92% of patients with distal lesions. Patients experienced similar postoperative length of stay (median: proximal, 13 days vs. distal, 13 days; p=0.64) and operative mortality (30-day: proximal, 4% vs. distal, 3%; p=1.0, Fishers). Margin positive rates were similar (proximal, 23% vs. distal, 15%; p=0.20). Estimated five-year DSS for all patients was 35%. Tumor location (proximal vs. distal) was not associated with five-year estimated DSS (proximal, 29% vs. distal, 43%; p=0.44). Factors associated with five-year DSS included stage at presentation (node negative, 42% vs. node positive, 22%; p=<0.001), differentiation (papillary, 53% vs. non-papillary, 27%; p=0.01), and margin status (margin negative 42% vs. margin positive 27%; p<0.001). CONCLUSIONS: These results suggest that patients with resected proximal and distal cholangiocarcinoma will experience similar operative outcomes and DSS.