Heparin-induced thrombocytopenia is a serious complication of heparin use. Treatment includes discontinuation of heparin and initiation of alternative anticoagulation therapy. In extracorporeal membrane oxygenation anticoagulation is mandatory, and direct thrombin inhibitors (DTIs) have been approved in these cases. However, the use and monitoring of DTIs in extracorporeal membrane oxygenation patients is not well described. DTI use is also complicated by the imprecision of available monitoring tests and currently recommended dosing has been shown to result in a supratherapeutic anticoagulative state. This case report describes the successful use of the DTI argatroban as an alternative anticoagulant in a patient with heparin-induced thrombocytopenia requiring extracorporeal membrane oxygenation support.