We report a case of perforation of the esophagus associated with mediastinitis and pneumomediastinum during endoscopic treatment. The patient was successfully treated by means of nonsurgical computed tomography-guided mediastinal drainage. Esophagoscopy demonstrated a scar on the 14th day at the perforation site. This nonsurgical treatment with computed tomography-guided mediastinal drainage is proposed as a less invasive treatment for iatrogenic perforation of the esophagus.