Many studies have reported 5-year survival data after pancreaticoduodenectomy for periampullary adenocarcinoma. This study evaluates 10-year survival in patients surviving 5 years after initial surgery. We reviewed all patients undergoing pancreaticoduodenectomy for periampullary adenocarcinoma from April 1970 to July 1999 at a single institution. All 5-year survivors were identified, and their subsequent 5-year survival was compared with the actuarial survival of the general population starting at 70 years of age. Nine hundred fifteen patients underwent pancreaticoduodenectomy for periampullary adenocarcinoma. Follow-up was complete on 890 patients. There were 201 (23%) 5-year survivors with a median age of 65 years at initial surgery; 51% were male and 92% were Caucasian. For the 5-year survivors, the carcinoma origin was pancreatic in 46%, ampullary in 25%, distal bile duct in 17%, and duodenal in 12%. For all 5-year survivors, the subsequent 5-year actuarial survival rate was 65%, with a median survival after achieving the 5-year landmark of 7.9 additional years. The subsequent 5-year survival by site of tumor origin was 55% for pancreatic, 66% for ampullary, 74% for bile duct, and 85% for duodenal cancer. For the age-matched population, the 5-year survival rate was 87% (P<.001 when compared with those with all periampullary cancers). While the 5-year survival rate for all patients with resected periampullary adenocarcinoma is only 23%, these data imply that attainment of the 5-year survival landmark carries with it an improved survival for the subsequent 5 years. While the survival rate was less than that of the age-matched population, 65% of 5-year survivors survived 5 more years, bringing them to the 10-year postresection landmark.