RATIONALE: Extracorporeal membrane oxygenation (ECMO) in multiple trauma patients with post-traumatic respiratory failure can be quite challenging because of the need for systemic anticoagulation, which may lead to excessive bleeding. In the last decade, there is a growing body of evidence that veno-venous ECMO (VV-ECMO) is lifesaving in multiple trauma patients with acute respiratory distress syndrome, thanks to technical improvements in ECMO devices. PATIENT CONCERNS: We report a case of a 17-year-old multiple trauma patient who was drunken and had confused mentality. DIAGNOSES: She was suffered from critical respiratory failure (life-threatening hypoxemia and severe hypercapnia/acidosis lasting for 70 minutes) accompanied by cardiac arrest and trauma-induced coagulopathy during general anesthesia. INTERVENTIONS: We decided to start heparin-free VV-ECMO after cardiac arrest considering risk of hemorrhage. OUTCOMES: She survived with no neurologic sequelae after immediate treatment with heparin-free VV-ECMO. LESSONS: Heparin-free VV-ECMO can be used as a resuscitative therapy in multiple trauma patients with critical respiratory failure accompanied by coagulopathy. Even in cases in which life-threatening hypoxemia and severe hypercapnia/acidosis last for >1 hours during CPR for cardiac arrest, VV-ECMO could be considered a potential lifesaving treatment.