Twenty patients with adenocarcinoma of the pancreas underwent a regional pancreatectomy, including resection of the pancreas, regional lymphadenectomy, duodenectomy, antrectomy, and sleeve resection of the portal vein. Three patients required mesenteric arterial reconstruction. Adjunctive radiotherapy was administered to 17 patients, with 11 patients receiving intraoperative radiation and six patients receiving postoperative external-beam-radiation. Complications developed in 11 patients (55%), including infectious and septic events (five patients), biliary or enteric fistulas (two patients), mesenteric vascular thrombosis (two patients), and other complications (two patients). Four patients (20%) suffered treatment-related deaths. The overall median survival was 12.0 months. Survival at one year was 50% and, at three years, 10%. Two patients died of causes unrelated to cancer at 18 and 39 months, and one patient remains alive and free of disease 50 months following therapy. Morbidity and survival did not differ among patients who received intraoperative, conventional postoperative, or no radiation therapy. Although occasional patients may benefit with survivals of longer than three years, regional pancreatectomy carries major morbidity and produces little survival benefit for most patients with pancreatic cancer.