Closure of post‐endoscopic submucosal dissection (ESD) duodenal artificial ulcer is not common in the clinical setting. We consider that post‐ESD ulcer closure by an over‐the‐scope‐clip (OTSC) method is one of the most effective ways to prevent delayed perforation. We report here two cases of mucosal duodenal cancer in a 65‐year‐old woman and in a 78‐year‐old man. Pathological examinations of the resected specimens revealed well‐differentiated adenocarcinomas. In these two clinical cases, we successfully carried out complete closures of post‐ESD duodenal ulcer using OTSC without any complications.