OBJECTIVE: This single-institution experience retrospectively reviews the outcomes in a group of patients treated 5 or more years ago by pancreaticoduodenectomy for periampullary adenocarcinoma. SUMMARY BACKGROUND DATA: Controversy exists regarding the benefit of resection for periampullary adenocarcinoma, particularly for pancreatic tumors. Many series report only Kaplan-Meier actuarial 5-year survival rates. There are believed to be discrepancies between the actuarial 5-year survival data and the actual 5-year survival rates. METHODS: From April 1970 through May 1992, 242 patients underwent pancreaticoduodenal resection for periampullary adenocarcinoma at The Johns Hopkins Hospital. Follow-up was complete through May 1997. All pathology specimens were reviewed and categorized. Actual 5-year survival rates were calculated. The demographic, intraoperative, pathologic, and postoperative features of patients surviving > or =5 years were compared with those of patients who survived <5 years. RESULTS: Of the 242 patients with resected periampullary adenocarcinoma, 149 (62%) were pancreatic primaries, 46 (19%) arose in the ampulla, 30 (12%) were distal bile duct cancers, and 17 (7%) were duodenal cancers. There was a 5.3% operative mortality rate during the 22 years of the review, with a 2% operative mortality rate in the last 100 patients. There were 58 5-year survivors, 28 7-year survivors, and 7 10-year survivors. The tumor-specific 5-year actual survival rates were pancreatic 15%, ampullary 39%, distal bile duct 27%, and duodenal 59%. When compared with patients who did not survive 5 years, the 5-year survivors had a significantly higher percentage of well-differentiated tumors (14% vs. 4%; p = 0.02) and higher incidences of negative resection margins (98% vs. 73%, p < 0.0001) and negative nodal status (62% vs. 31%, p < 0.0001). The tumor-specific 10-year actuarial survival rates were pancreatic 5%, ampullary 25%, distal bile duct 21%, and duodenal 59%. CONCLUSIONS: Among patients with periampullary adenocarcinoma treated by pancreaticoduodenectomy, those with duodenal adenocarcinoma are most likely to survive long term. Five-year survival is less likely for patients with ampullary, distal bile duct, and pancreatic primaries, in declining order. Resection margin status, resected lymph node status, and degree of tumor differentiation also significantly influence long-term outcome. Particularly for patients with pancreatic adenocarcinoma, 5-year survival is not equated with cure, because many patients die of recurrent disease >5 years after resection. Images Figure 1.