Objective: To investigate the prognostic factors in patients with adenocarcinoma of the ampulla of Vater after pancreaticoduodenectomy. Methods: The clinical and pathological data of patients with adenocarcinoma of the ampulla of Vater undergoing pancreaticoduodenectomy from January 2007 to December 2014 were reviewed. The influential factors for postoperative survival of the patients were analyzed. Results: In the entire group of patients, the postoperative 1-, 3- and 5-year survival rate was 87.5%, 64.3% and 54.5% respectively. Univariate analysis showed that preoperative level of total bilirubin, direct bilirubin, CEA, CA19-9 and CA242 and degree of tumor differentiation, depth of infiltration, lymphatic metastasis, tumor stage, involvement of pancreas, neural invasion and postoperative adjuvant therapy were influential factors for survival. Multivariate analysis indicated that preoperative CEA level and depth of infiltration were independent prognostic factors (both P<0.05). Conclusion: Multiple factors are related to the prognosis of patients with adenocarcinoma of the ampulla of Vater after pancreaticoduodenectomy, and among them, the CEA level and the depth of infiltration are the most important indicators for estimating the prognosis of the patients.