Peroral endoscopic myotomy (POEM) is a groundbreaking procedure for treating esophageal achalasia, and many reports from various facilities have described its safety and efficacy. However, there have been few reports on adverse events. Here, we report a case of a patient with mediastinitis caused by delayed mucosal damage after POEM. This case was the most severe among all POEM cases at our hospital. A 58-year-old man had experienced dysphagia and chest tightness since he was around 50 years old. At a previous hospital, he had been diagnosed with nonerosive reflux disease and had undergone fundoplication. As his symptoms did not improve, he was referred to our department. POEM was able to be finished but a stable visual field could not be maintained throughout procedure because of strong esophageal contractions. From findings of endoscopy and esophagography after POEM, the patient was diagnosed mediastinitis caused by delayed esophageal perforation. In this case, conservative treatment (fasting, antibiotic therapy, and enteral feeding) was successful. However, the option to administer surgical treatment, such as drainage, must not be overlooked.