This report concerns 348 pancreatoduodenectomies, including 13 total pancreatectomies. Operative mortality over 30 years was 15%, operative mortality since 1962, 10%. Precise factors influencing operability, mortality, morbidity, and long-term palliation or cure are emphasized. The necessity for making a distinction among tumors arising in the ampulla of Vater, the intrapancreatic portion of the common bile duct, and the duodenum surrounding the papilla of Vater and carcinomas arising in the head of the pancreas is the most important factor in the approach to periampullary malignant tumors. Even with this large experience, the impression of the operating surgeon at the time of resection was incorrect in 10% of the patients in whom a reons who do not resect carcinomas arising in the head of the pancreas and who may have had less experience in this specialized field may be rejecting an even larger per cent of patients with more favorable periampullary malignant tumors. The influence of previous exploration, manipulation, and biopsy on morbidity, mortality, and survival is discussed. The significance of nodal involvement and residual tumor at the neck of the pancreas and the point of division of the common bile duct and the uncinate process is discussed. These data justify continued selective application of pancreatoduodenectomy for periampullary cancer and identify areas where further improvement can be made.