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William S. Halsted published his report of local excision of a periampullary neoplasm in 1899. The patient subsequently died of metastatic disease. During the past nearly 100 years there have been tremendous advancements in the understanding of physiology, anesthetic and perioperative care, nutritional support, and surgical technique. These have served to improve short- and long-term survival for patients with these periampullary tumors. Despite the many advances in this arena there remains significant controversy as to how best approach these tumors. In this brief discussion we present the data from the most recent analysis of the experience with pylorus-preserving pancreatoduodenectomy (PPPD) for periampullary neoplasms and a rationale for this approach based on the experimental and clinical data that are available. On the basis of analysis of 106 patients who have undergone PPPD for cancer over a 13-year period and the rapidly expanding world experience with this operation, we conclude that PPPD is an adequate operation for periampullary carcinoma, but has not been proven to be a superior operation to the “standard Whipple” procedure in controlled trials.