One hundred six pancreaticoduodenectomies, including 10 cases done for benign disease were reviewed, retrospectively, and 51 factors analyzed. There is a significant difference in survival based upon final pathologic diagnosis. Five-year survivals were 0% for adenocarcinoma of the pancreas, 38% for duodenal carcinoma, 24% for CBD carcinoma, 30% for ampullary carcinoma, 24% for other cancers not considered part of the ampullary region, and 100% for those with benign disease (X2 = 24.66, df = 5, p = 0.0002). Four statistically significant poor prognostic factors were identified, including age >51 years, serum bilirubin level >6 mg/dl, SGOT > 100, and a previous drainage procedure. Results of this study seem to indicate that the pancreaticoduodenectomy has limited indications in adenocarcinoma of the pancreas, but remains the procedure of choice for all other periampullary lesions including suspicious lesions with a negative biopsy at the time of surgery.