Background: Major trauma is a leading cause of death, particularly amongst young patients. New strategies in management are needed to improve the poor outcome of severe trauma. We report our initial experience with extracorporeal life support (ECLS) as a rescue therapy in severe multiple trauma patients with refractory cardiopulmonary failure. Objectives: The purpose of this study was to identify the pre-ECLS patient characteristics predicting appropriateness ECLS treatment. Methods: From December 2008 to May 2013, 420 multiple trauma patients were treated at our tertiary level referral trauma center. Our ECLS team was alerted on 35 and applied ECLS in 20 adult trauma patients. In 16 patients with cardiopulmonary failure with refractory shock, we adopted a veno-arterial ECLS; in 4 patients with isolated refractory acute respiratory failure, we used venovenous ECLS. Results: ECLS was initiated at a mean of 324.15 ± 197.8 (110 - 950) min from initial trauma. In 4 patients, ECLS treatment failed due to an incapability to maintain adequate ECLS flow and patient perfusion. In the other 16 patients efficiently supported by ECLS, the Cardiac Index, mean arterial pressure, lactate concentration, PaO2, PaCO2, and pH showed significant improvement with normal values reached at 3.2 ± 1.5 hours. Seven (43.7%) patients in the ECLS-Success Group donated organs, 2 patients (22.2%) died due to septic multi organ failure (MOF), and 7 (77.7%) patients were discharged from the hospital. ECLS was suitable and successful in patients with a significantly lower injury severity score, lower blood lactate level, lower number of blood units given, and significantly higher pH and Hb. Conclusions: From our data, ECLS seems to be a valuable option to resuscitate severe trauma patients when conventional therapies are insufficient: it is safe, feasible and effective in providing hemodynamic support and blood gas exchange. Our data permitted us to identify strong predictors of ECLS non-suitability and success in multiple trauma patients; these might be helpful in deciding whether ECLS should be used or not. Future improvements in materials and techniques are expected to make ECLS even easier and safer to manage, leading to a further extension of its use in disastrously injured patients