Abstract: Objective：To investigate the feasibility and safety of endoscopic full-thickness resection (EFR) for duodenal submucosal tumors (SMTs). Methods：The retrospective study included a total of 12 patients with duodenal SMTs who underwent EFR from April 2015 to December 2017 in our hospital. Characteristics of the tumors, clinical data, treatment outcomes, and complications were analyzed. Results：Twelve patients with duodenal SMTs successfully underwent EFR. The average tumor diameter was (3.375±0.4) cm, all of the tumors were closed to the muscularispropria, and four presented exophytic growth. The average operation time was 40.5 min. Massive bleeding occurred in two cases during the procedure. Two patients experienced postoperative delayed hemorrhage, one was managed conservatively, the other one was also managed successfully by endoscopic methods. Four patients developed severe upper central abdominal pain, all of them were relieved by symptomatic treatment. Pathology reports showed that, six lesions were stromal tumors, which was the main type. Conclusions：EFR of duodenal SMTs is a safe and effective technique, which could be used as one of the options for endoscopic minimally invasive treatment of large SMTs, especially for extraluminal growth lesions.