OBJECTIVE To assess the adequacy of pylorus-preserving pancreatoduodenectomy (PPPD) as a definitive surgical treatment for primary malignant diseases of the periampullary region. METHODS Retrospective review of the clinical records of patients undergoing PPPD for malignant diseases of the periampullary region. Median and 5-year actuarial survival by type and stage of cancer were determined. Survival data from this study were compared with those of patients undergoing a conventional Whipple operation. METHODS Lahey Clinic, Burlington, Mass. METHODS One hundred six patients undergoing PPPD for primary malignant disease of the periampullary region between November 1979 and June 1992. METHODS Pylorus-preserving pancreatoduodenectomy was performed with curative intent in the 106 patients. Ninety-five patients underwent proximal pancreatectomy; 11 patients, total pancreatectomy. Resection of the portal vein was performed in 10 patients. METHODS Long-term survival following PPPD was analyzed with respect to the type and stage of cancer. Median follow-up was 30 months (range, 6 to 156 months). RESULTS Five-year actuarial survival rates were 45.4% for patients with ampullary adenocarcinoma; 6.6%, with pancreatic ductal adenocarcinoma; 33.3%, with distal bile duct adenocarcinoma; 75%, with pancreatic islet cell adenocarcinoma; and 0%, with pancreatic cystadenocarcinoma. An early cancer stage was associated with more favorable survival for ampullary and distal bile duct adenocarcinomas. For pancreatic ductal adenocarcinoma only, tumors less than 2 cm were associated with better survival. Duodenal resection margins were free of disease in all patients, while peripancreatic and retroperitoneal extension of the tumor was found in 20%. CONCLUSIONS For patients with periampullary malignant disease, long-term survival following PPPD is similar to that following a conventional Whipple operation. The potential benefits of hemigastrectomy with perigastric lymphadenectomy are frequently obviated by the presence of positive margins and lymph nodes elsewhere, ie, in the retroperitoneum. We advocate PPPD as the procedure of choice for locally resectable malignant disease of the periampullary region, provided the duodenal margin is viable and tumor free.