Survival of patients with adenocarcinoma of the duodenum depends on the ability to perform a complete resection and the tumor stage Retrospective case series. Tertiary care referral center. A cohort of 101 consecutive patients (mean age, 62 years), undergoing surgery for duodenal adenocarcinoma from January 1, 1976, through December 31, 1996. Patients with ampullary carcinoma were specifically excluded. Mean duration of follow-up was 4 years. Surgery was curative in 68 patients (67%) and palliative in 33 patients (33%). Of the curative group, 50 patients (74%) underwent radical surgery, ie, 30 (60%), pancreaticoduodenectomy; 15 (30%), pylorus-preserving pancreaticoduodenectomy; and 5 (10%), total pancreatectomy. A more limited resection procedure was used in 18 patients (26%) involving a segmental duodenal resection in 15 (83%) and a transduodenal excision in 3 (17%). patient survival, and correlation with patient and tumor variables using univariate and multivariate analysis. Actuarial 5-year survival for the curative group was 54%. Only 1 patient in the unresected group survived beyond 3 years. Nodal metastasis (P = .002), advanced tumor stage (P<.001), positive resection margin (P = .02), and weight loss (P<.001) had a significant negative impact on survival in multivariate analysis. Tumor grade, size, and location within the duodenum had no impact on survival. Patient age and tumor depth of invasion influenced survival in univariate analysis, but lost their prognostic significance in multivariate analysis. Metastasis to lymph nodes, advanced tumor stage, and positive resection margins are associated with decreased survival in patients with duodenal adenocarcinoma. An aggressive surgical approach that achieves complete tumor resection with negative margins should be pursued. Pancreaticoduodenectomy is usually required for cancers of the first and second portion of the duodenum. Segmental resection may be appropriate for selected patients, especially for tumors of the distal duodenum.