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To trace the evolution of pancreaticoduodenectomy from the decade of the 1960s through the first decade of the new Millenium, through the experience of one surgeon doing 1000 consecutive operations.A regional resection of the head of the pancreas was first performed successfully by Kausch in 1909. The operation was popularized by Whipple in 1935, who reported 3 pancreaticoduodenectomies. Because of a hospital mortality of approximately 25%, the operation was performed infrequently until the 1980s. From the 1980s on, experience with this complex alimentary tract operation increased, and high-volume centers developed. This resulted in a significant drop in hospital mortality and allowed institutions and individuals to gain large experiences.Between March 1969 and May 2003, 1000 consecutive pancreaticoduodenectomies were performed by a single surgeon. A retrospective review of a prospectively maintained database was performed to determine the management and outcome of these patients, as well as to document the evolution of this operative procedure over 5 decades.The median operative time decreased significantly over the decades, being 8.8 hours in the 1970s and 5.5 hours during the 2000s. Postoperative length of stay dropped from a median of 17 days in the 1980s to 9 days in the 2000s. There were only 10 postoperative/hospital deaths, for a mortality of 1%. A total of 405 patients underwent pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas. Overall 5-year survival was 18%; for the lymph node-negative patients, it was 32%; and for node-negative, margin-negative patients, it was 41%.Pancreaticoduodenectomy has become a commonly performed operation in many tertiary care centers. Operative time, blood loss, and length of stay have dropped substantially. The operation has become safe, with a low hospital mortality. It has become an effective operation for pancreatic cancer in those patients in whom their tumor is margin negative and node negative.