Cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) are both mechanical circulatory support technologies that augment the native heart and/or lung function. They involve drainage and reinfusion of blood while performing extracorporeal gas exchange. 1 In both devices, contact between patient blood and the non-endothelialized surface of the circuit triggers an inflammatory response and pro-coagulation cascade. 2–5 As a result, prophylactic anticoagulation is integral to prevent catastrophic thrombosis of the circuitry. In rare instances, there exist contraindications to heparin use, necessitating alternative management strategies. 6 In this review, we will examine heparin contraindications in mechanical circulatory support and summarize alternative approaches to anticoagulation in these circumstances.