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Heparin is the widely used anti-coagulation strategy for patients on extracorporeal membrane oxygenation (ECMO). Nevertheless, heparin-induced thrombocytopenia (HIT) and acquired anti-thrombin (AT) deficiency preclude the use of heparin requiring utilization of an alternative anticoagulant agent. Direct thrombin inhibitors are being proposed as potential alternatives with argatroban as one of the main agents. We aimed to review the evidence with regard to safety and efficacy of argatroban as a potential definitive alternative to heparin in the adult patient population undergoing ECMO support.