Esophageal perforation and mediastinal gas gangrene developed in a 55-year-old male after the endoscopic ethanol injection of a Mallory-Weiss ulcer. Initially, extensive gangrene of the esophagus and the mediastinum was treated by esophagectomy; however, an abundance of Clostridium perfringens in the Gram stain verified the presence of gas gangrene. Subsequently, the patient was transferred to a hyperbaric oxygen center, wherein a total of seven hyperbaric treatments were administered. The patient survived, and 4 months later, after having undergone several reoperations because of pleural empyema, mediastinal abscess, splenic rupture, and acalculous cholecystitis, was discharged and is still surviving.