The operative management of 200 patients with pancreatic and periampullary cancer was reviewed. Patients with metastatic disease and biliary obstruction are best treated by the nonoperative techniques of biopsy and internal biliary drainage if technically feasible. For patients who undergo exploration and are found to be candidates for a bypass procedure, both biliary and gastroduodenal bypass should be performed. Lymph node involvement and age of the patient were found to be significant variables in determining the candidates suitable for curative resection. A definite incidence of multicentricity was found in patients undergoing total pancreatectomy for ductal carcinoma of the pancreas; however, significant problems with diabetic management arose from this procedure. The primary site of the lesion as well as the intelligence and socioeconomic background of the patient should dictate the type of resection employed. Pancreatoduodenectomy (Whipple procedure) is recommended for periampullary cancers other than pancreatic carcinoma, while total pancreatectomy may be appropriate in selected patients. However, there has been no evidence thus far in this early trial with total pancreatectomy that more complete resection of the pancreas leads to longer survival.