Endoscopic treatment for superficial non-ampullary duodenal tumors is technically difficult and challenging due to the anatomical characteristics of the duodenum. It is frequently complicated by procedural accidents, such as perforation. Surgical repair has long been the standard treatment for acute iatrogenic gastrointestinal perforation. However, endoscopic closure has recently emerged as an attractive alternative. In the patient presented herein, the over-the-scope-clipping system (OTSC system) was found to be useful for closing a duodenal perforation that had occurred during endoscopic submucosal dissection. For endoscopists who perform endoscopic treatment of the duodenum, endoscopic closure with the OTSC system is considered to be a technique that is necessary to master.