A 74-year-old female, who was diagnosed with superficial esophageal cancer, underwent endoscopic submucosal dissection (ESD) at another hospital, but a perforation occurred during the procedure. The perforation was closed with endoscopic clips, and the ESD was halted. The patient was referred to our hospital, and ESD was retried. There was severe fibrosis around the lesion, and injections into the submucosal layer were difficult. In addition, it was not possible to identify the submucosal layer, and making an oral-side incision caused a large perforation along the incision line. As continuing the submucosal dissection with an endoknife was considered difficult, the lesion was finally resected with hybrid ESD using a snare. The perforation was closed using polyglycolic acid (PGA) sheets and fibrin glue. Endoscopy performed 6 days later showed that the defect had been closed, and no contrast leakage was detected. Follow-up endoscopy conducted 3 months after the ESD showed ulcer healing at the dissection site and scar formation, but no residual tumor or esophageal stricture was noted. Our experience suggests that the use of PGA sheets with fibrin glue is a feasible, safe, and effective way of treating large esophageal perforations during ESD.