Background Patients with familial adenomatous polyposis (FAP) are prone to developing duodenal adenoma and cancer. Optimal surveillance and management of these adenomas are not well established. Objective We assessed the outcome of FAP patients undergoing intense multimodal surveillance and subsequent endoscopic resection of advanced lesions. Patients Eighty consecutive FAP patients enrolled during 2001 to 2011 from the Familial Cancer Clinic of a tertiary hospital as part of routine surveillance. Design Case series, prospective in years 2006 to 2011 and retrospective in years 2001 to 2006. Setting and Intervention Patients were followed by annual forward-view and/or side-view upper endoscopy. A biopsy sample was obtained from visible lesions and normal papillae. Ampullary adenomas were further assessed by EUS to determine dimensions and resectability. Advanced adenomas (size â‰¥ 10 mm, villous type, high-grade dysplasia) underwent endoscopic ampullectomy or polypectomy and continued surveillance. Main Outcome Measurements Detection of advanced adenomas by endoscopy and EUS, endoscopic maintenance of duodenum free of advanced adenoma and cancer. Results Patients (38 men and 42 women, mean age 32.68 ± 13.60) were followed 7.2 years and underwent 5.36 diagnostic studies on average. Thirty-eight patients had ampullary adenomas. Advanced adenoma was diagnosed by endoscopy in 10 patients. Importantly, EUS upstaged 9 additional patients to advanced adenoma and downstaged 1, thus altering the treatment course in 36% of patients performing EUS. Endoscopic ampullectomy was performed in 15 patients. Adenoma recurred in 10. Five remained nonadvanced and 5 in advanced stages: 3 were successfully retreated endoscopically and 2 ultimately required surgery for residual adenoma. Advanced nonampullary adenomas were successfully resected endoscopically in 23 patients. No patient had duodenal cancer during the study period. Limitations Limited follow-up period, young age group, uncontrolled study. Conclusions In an intense surveillance program for FAP patients, both endoscopy and EUS were key in accurate selection of advanced adenomas for endoscopic resection. During a 10-year period, only 2 patients required elective surgery and no cancer was observed.