This single-institution retrospective analysis reviews the management and outcome of patients with surgically treated adenocarcinoma of the duodenum. Between February 1984 and August 1996, fifty-five patients with adenocarcinoma of the duodenum underwent surgery at The Johns Hopkins Hospital. Univariate analysis was performed to identify possible prognostic indicators. Curative resection was performed in 48 patients (87%): 35 of these patients (73%) underwent a pancreaticoduodenectomy (PD), whereas 27% (n = 13) underwent a pancreas-sparing duodenectomy (PSD). Patients undergoing PD were comparable to those undergoing PSD with respect to demographic factors, presenting symptoms, and tumor pathology. The remaining 13% of patients (n = 7) were deemed unresectable at the time of surgery and underwent biopsy and/or palliative bypass. PD was associated with an increase in postoperative complications when compared to PSD (57% vs. 30%), but this difference was not statistically significant. One perioperative death occurred following PD (mortality 2.9%). The overall 5-year survival rate for the 48 patients undergoing potentially curative resection was 53%. Negative resection margins (P <0.001), PD (P <0.005), and tumors in the first and second portions of the duodenum (P <0.05) were favorable predictors of long-term survival by univariate analysis. Nodal status, tumor diameter, degree of differentiation, and the use of adjuvant chemoradiation therapy did not influence survival. These data support an aggressive role for resection in patients with adenocarcinoma of the dueodenum