Out of 36 consecutive patients who underwent a pancreatoduodenectomy for carcinoma of the ampulla of Vater, eight patients (long-term survivors) survived more than 5 years after surgery, while eight other patients (short-term survivors) survived less than 12 months after intervention. Both the eight long-term survivors and eight short-term survivors were compared clinicopathologically. The long-term survivors did have some preferable factors such as a high value of peripheral lymphocytes, a low concentration of carcinoembryonic antigen, a small protruding tumor, a shallow depth of invasion, a well-differentiated histopathologic type, an infrequent venous invasion, and no perineural infiltration. However, these differences were not significant. A multivariate regression analysis regarding the 18 prognostic variables showed that both perineural invasion and the grade of histopathologic differentiation were significant parameters. Out of the eight long-term survivors, three patients lived more than 10 years while another died from ampullary carcinoma 74 months after surgery. Pancreatoduodenectomy not only produces long-term survivors but can also effect a complete cure in patients with ampullary carcinoma. A long clinical follow-up of more than 5 years after surgical intervention is thus warranted.