This large and multi-center registry study shows that patients with obesity class II or more (body mass index (BMI) ≥ 35 kg/m2) undergoing extracorporeal membrane oxygenation for respiratory failure have decreased mortality risk and decreased hospital length of stay, despite an increased risk of cardiovascular, device-related, and renal complications. The association between BMI and these outcomes is non-linear and no upper limit of BMI indicating futility was identified.