Extracorporeal membrane oxygenation (ECMO) is a form of cardiorespiratory support, and is being increasingly used to support refractory heart and respiratory failure. It involves draining blood from the vascular system, which is then circulated outside the body by a mechanical pump and then later reinfused back into the circulation. The blood that is circulated outside the body comes in contact with a large surface area of non-endothelial biosurface. This exposure leads to a pro-thrombotic state, and hence anticoagulation is required. Unfractionated heparin is the most commonly used anticoagulation in most ECMO centers, but it does require close monitoring. Despite the advances made, hemostasis remains a challenge for physicians who manage patients on ECMO.