<p><b>OBJECTIVE</b>To discuss the significance of a positive ductal margin and evaluate the prognostic factors related to surgical resection for middle and distal bile duct carcinoma.</p><p><b>METHODS</b>A retrospective clinicopathological analysis of 79 patients who had undergone surgical resection for middle or distal bile ductal cancer between January 1990 and December 2006 was conducted. The surgical procedures consisted of pancreatoduodenectomy in 46 patients, bile duct resection in 25 patients, bile duct resection plus hepatectomy in 6 patients, and bile duct resection with partial resection of portal vein in 2 patients. In 74 patients, 5 patients were excluded because they died after surgery without being discharged from the hospital, 15 clinicopathologic factors were evaluated using univariate and multivariate analysis.</p><p><b>RESULTS</b>The overall 5-year survival rate and the median survival time was 30.7% and 36 months, respectively. Sixteen of 74 patients (20.3%) were determined to have positive ductal margins on the final pathological examination. As a result, hepatic-side ductal margin, duodenal-side ductal margin and both was found to be positive in 6, 3 and 2 patients, respectively. Five patients had positive radial margins. The 5-year survival rate was 34.4% in 58 patients without microscopic residual disease (R0), and 15.5% in 16 patients with microscopic residual tumor (R1). The ductal recurrence rate of 16 patients with R1 resection was higher than 58 patients with R0 resection (62.5% vs. 17.2%, chi(2) = 13.024, P < 0.01). The 1-, 3-, and 5-year survival rates were better in the patients with R0 (92.5%, 56.7%, and 34.4%, respectively) than those in the patients with R1 resection (75.0%, 23.2%, and 15.5%, respectively) (P < 0.05). Twelve patients received postoperative adjuvant therapy. The 5-year survival rate was not significantly different between patients with postoperative adjuvant therapy and those without (18.2% vs. 31.8%, P = 0.221). The preoperative serum level of hemoglobin, pathological differentiation grade, the depth of neoplastic invasion, lymph node metastasis, R1 resection, and TNM stage were significant prognostic factors on the univariate analysis. Multivariate analysis revealed that lymph node metastasis and R1 resection were the independent prognostic factors.</p><p><b>CONCLUSIONS</b>In the treatment of middle and distal bile duct cancer, radical resection should be made to obtain a tumor-free margin. An aggressive surgical approach may improve the survival for middle bile duct cancer. Adjuvant therapy needs to be further developed.</p>