BACKGROUND Endoscopic submucosal resection (ESD) and endoscopic mucosal resection (EMR) are well established as curable and safety procedures for treating superficial tumors of the stomach, esophagus and colon. However, a majority of endoscopic resection strategies for non-ampullary superficial duodenal tumors (NASDTs) remains undefined. The aim of this study was to clarify which was the right method for NASDT treatment - EMR or ESD. CONCLUSIONS We analyzed 129 consecutive endoscopic resection (74 ESD and 55 EMR) procedures performed with NADSTs and divided the ESD group into 49 large ESD groups (more than 20 mm in diameter) and 25 small ESD groups (less than 20 mm in diameter). With respect to the technical outcomes of EMR/ESD for small size NASDTs, EMR was safer than ESD, but its nature of curability was inferior to that of ESD. The rates of complication such as perforation or delayed bleeding were significantly higher in both ESD groups than in the EMR group. However, the prophylactic endoscopic closure of large mucosal defects after ESD was useful for resolving those complications. The limitations of our study were involvement of a single-center, limited sample size, short follow-up duration and the retrospective design, which may have introduced selection bias. However, the present findings suggest that adequate endoscopic treatment strategy for NASDTs can lead to favorable outcomes and an excellent prognosis. Key Message: It is necessary to select EMR or ESD adequately for R0 resection of small NASDTs, according to their size and location. For large NASDTs, duodenal ESD with essential management is feasible and useful as a therapeutic procedure.