Pneumomediastinum is rare but potentially life-threatened and needs rapid diagnosis and adequate treatment. The etiology varies extensively. We report the first case of pneumomediastinum induced by heroin inhalation and exacerbated by ventilator-induced barotrauma. We approached the case by chest radiography, computed tomography of chest and bronchoscope. We successfully treated the case with skin incision and drainage of air. Pneumomediastinum induced by heroin inhalation is rare and should be taken into differential diagnosis in drug-abused patients who suffer from chest pain, dyspnea, and subcutaneous emphysema of upper trunk. We should also be alert to the patients who are supported by ventilator to avoid exacerbation of pneumomediastinum by ventilator-induced barotrauma.