Rationale: Surgery is the treatment of choice for esophageal cancer. Since the 1990s, minimally invasive esophagectomy (MIE) has been developed using videoscope. Although MIE lowers mortality by reducing postoperative complications, the risk of carbon dioxide (CO 2 ) insufflation related complications still exists.Patient concerns: A 56-years-old male patient underwent elective MIE. The patient (body mass index, 15 kg/m 2 ) had wellcontrolled hypertension, cardiomegaly, and severe emphysematous lungs. He had iatrogenic pneumothorax during central venous catheterization 3 weeks prior; however, the pneumothorax was resolved before surgery.Diagnosis: During thoracoscopic surgery, respiratory acidosis was not corrected despite rapid respiratory rate and positive end-expiratory pressure. Intrathoracic CO 2 pressure was lowered from 12 to 8 mm Hg, and laparoscopic surgery was performed through the diaphragm in the reverse Trendelenburg position. In 15 minutes at this position, pulseless electrical activity with respiratory failure and high peak inspiratory pressure developed.Interventions: CO 2 insufflation was stopped and drained as soon as hypotension developed. The patient was placed in the supine neutral position, and cardiopulmonary circulation was restored without further treatment.Outcomes: After the pneumomediastinum event, surgery was successfully performed. Respiratory acidosis due to CO 2 insufflation was not corrected during surgery and the patient was transferred to intensive care unit without extubation. After 14 days, the patient was discharged without cardiopulmonary complications. However, the patient expired 2 years later due to cardiovascular disease.Lessons: In MIE, there is always a risk of catastrophic tension pneumomediastinum along with intravascular volume depletion, surgical position, and ventilatory strategy depending on the surgical characteristics.Abbreviations: CO 2 = carbon dioxide, MIE = minimal invasive esophagectomy.