For the treatment of tumor lesions of the papilla of Vater (papilla), it is required, in addition to a sufficient pathohistologic investigation, to achieve an adequate pretherapeutic tumor staging, which allows a decision-making toward the appropriate treatment (surgical intervention, papillectomy, papillotomy) according to the patients specific finding. These requirements can be fulfilled by endoscopic ultrasonography (EUS).The aim of the study was to investigate feasibility, treatment results & outcome of endoscopic papillectomy.Methods: Through a defined time period, all consecutive patients with tumor-like lesions of the papilla, who were considered for endoscopic papillectomy, were enrolled in this systematic bicenter case-controlled study. The patients were subdivided into 4 groups according to endoscopic & EUS findings as well as pathohistologic diagnosis. Feasibility & treatment results were characterized by R0 resection rate, morbidity (e.g., rate & spectrum of complications) & mortality; outcome was assessed by recurrence rate & tumor-free survival.Results: From 1996-2003, 58 patients underwent endoscopic papillectomy. Main symptoms prompting to diagnostic were unclear abdominal pain in 50% & cholestasis in 44%. Overall, 54/58 patients (93.1%; sex ratio, males:females=25:29 [1:1.16]; mean age, 65years [range, 22-88years]) were enrolled. Prior to papillectomy, EUS was performed in 4/5 (79.6%; n=43) of patients. Group(Gr.) 1 (adenoma, n=24): 91.7% (n=22) with R0 resection; minor complications, 12.5% (n=3); tumor-free survival after a mean of 18.5months, 87.5%; recurrence, 12.5% (n=3). Gr.2 (carcinoma/neuroendocrine tumor, n=18): 55.6% (n=10) with R0 resection; tumor-free survival after a mean of 18months, 77.8% (n=14); recurrence, 22.2% (n=4). Gr.3 (adenomyomatosis, n=4). Gr.4 (primarily no introducible catheter into the papilla, n=8). The overall complication rate was 20.4% (n=11): Bleeding, n=3; pancreatitis, n=7; perforation, n=1 (mortality, 0%). Conclusion: EUS is a sufficient diagnostic tool to preoperatively clarify diseases of the papilla in conjunction with pathohistologic investigation of a specimen. Endoscopic papillectomy with curative intention is a feasible & safe approach to treat adenomas of the papilla of Vater. In high-risk patients with carcinoma of the papilla but no hints of deep infiltrating tumor growth, endoscopic papillectomy can be considered a reasonable treatment option with low risk & an approximately 80-% probability of no recurrence if an R0 resection can be achieved. In patients with jaundice & in case, the catheter can not be introduced into the papilla, papillectomy may help to get access to the bile duct.