Respiratory failure may complicate multiple trauma and can add significant morbidity, mortality, and cost to the care of such patients. We used extracorporeal life support (ECLS) to treat 24 patients with multiple trauma who, after their injury, developed respiratory failure refractory to conventional ventilatory management. Injuries in these patients were the result of motor vehicle crashes (16 patients), pedestrian versus car collisions (3 patients), gunshots (2 patients), stabs (1 patient), and a recreational vehicle crash (1 patient). Patients were placed on venovenous or venoarterial ECLS, using continuous systemic anticoagulation with heparin, and percutaneous cannulation where possible. Average time on ECLS was 287 +/- 43 hours (12 +/- 1.8 days). The major complication was bleeding, which occurred in 75% of patients. Fifteen patients survived to be discharged from the hospital (63% survival). Early intervention (mechanical ventilation < or = 5 days prior to ECLS) was associated with good outcome. Despite risks of anticoagulation in patients with multiple injuries, ECLS can be life-saving in cases of respiratory failure refractory to conventional mechanical ventilation.