AIM: To investigate endoscopic ultrasound (EUS) for predicting depth of mucosal invasion and to analyze outcomes following endoscopic and transduodenal resection. METHODS: Records of 111 patients seen at our institution from November 1999 to July 2011 with the postoperative pathological diagnosis of benign ampullary and duodenal adenomas were reviewed. Records of patients who underwent preoperative EUS for diagnostic purposes were identified. The accuracy of EUS in predicting the absence of muscular invasion was assessed by comparing EUS reports to the final surgical pathological results. In addition, the incidence of the post-operative complications over a period of 30 d and the subsequent long-term outcome (recurrence) over a period of 30 mo associated with endoscopic and transduodenal surgical resection was recorded, compared and analyzed. RESULTS: Among 111 patients with benign ampullary and duodenal adenomas, 47 underwent preoperative EUS for 29 peri-ampullary lesions and 18 duodenal lesions. In addition, computed tomography was performed in 18 patients, endoscopic retrograde cholangio-pancreatography in 10 patients and esophagogastroduodenoscopy in 22 patients. There were 43 patients with sporadic adenomas and 4 patients with familial adenomatous polyposis (FAP)/other polyposis syndromes. In 38 (81%, P < 0.05) patients, EUS reliably identified absence of submucosal and muscularis invasion. In 4 cases, EUS underestimated submucosal invasion that was proven by pathology. In the other 5 patients, EUS predicted muscularis invasion which could not be demonstrated in the resected specimen. EUS predicted tumor muscularis invasion with a specificity of 88% and negative predictive value of 90% (P < 0.05). Types of resection performed included endoscopic resection in 22 cases, partial duodenectomy in 9 cases, transduodenal ampullectomy with sphincteroplasty in 10 cases and pancreaticoduodenectomy in 6 cases. The main post-operative final pathological results included villous adenoma (n = 5), adenoma (n = 8), tubulovillous adenoma (n = 10), tubular adenoma (n = 20) and hyperplastic polyp (n = 2). Among the 47 patients who underwent resection, 8 (17%, 5 of which corresponded to surgical resection) developed post-procedural complications which included retroperitoneal hematoma, intra-abdominal abscess, wound infection, delayed gastric emptying and prolonged ileus. After median followup of 20 mo there were 6 local recurrences (13%, median follow-up = 20 mo) 4 of which were in patients with FAP. CONCLUSION: EUS accurately predicts the depth of mucosal invasion in suspected benign ampullary and duodenal adenomas. These patients can safely undergo endoscopic or local resection. © 2013 Baishideng. All rights reserved.