One hundred four consecutive patients who underwent radical resection for ampullary cancer between 1965 and 1989 were retrospectively reviewed. Frequent clinical findings included jaundice (67%), significant (greater than 10%) weight loss (42%), and anemia (27%). Eighty-seven patients (84%) underwent a subtotal pancreatectomy, and 17 patients (16%) underwent a total pancreatectomy. The postoperative mortality was 5.7% (six patients), and reoperation for postoperative complications was required in six patients. The 5- and 10-year survival rates were 34% and 25%, respectively. Eight patients died of tumor recurrence more than 5 years after resection. Patient survival was significantly impaired by microscopic lymphatic invasion, regional nodal metastasis, tumor grade, and the epithelium of origin. In a multivariate analysis, only microscopic lymphatic invasion significantly reduced patient survival. Radical resection for ampullary cancer can be performed with a low morbidity and mortality and should remain the procedure of choice for ampullary carcinoma.