Development of increasingly complex perfusion devices with bonded heparin allowed for significant improvement of thromboresistance of most basic components required for cardiopulmonary bypass. In his recent review of heparin-coated cardiopulmonary bypass circuits, Gravlee cited 91 references dealing with heparin-coated surfaces, and far more can be found if the search includes material technology or heparin-coated devices not designed for cardiopulmonary bypass (eg, ventricular assist devices, hemofilters, catheters). The present review is focused on long-term application of heparin-coated equipment in conjunction with basic work on heparin bonding relevant for extracorporeal membrane oxygenation. Experimental open chest cardiopulmonary bypass using heparin-coated equipment without systemic heparinization up to 36 hours has shown improved thromboresistance, and better platelet preservation was demonstrated for perfusion with heparin-coated cardiopulmonary bypass equipment up to 5 days in the experimental set-up. Similar findings were reported for roller pump perfusion with heparin-coated tubing and centrifugal pump perfusion with heparin-coated pump heads. More recently, heparin bonding was also made available for oxygenators with true membranes that preclude plasma leakage. The available knowledge on clinical applications of heparin-coated perfusion equipment is mainly based on short-term applications like ours, which now includes more than 300 patients. Reduced postoperative blood loss and as a result fewer transfusions were the main benefits of heparin-coated equipment allowing for perfusion with low systemic heparinization. There are only a few reports on long-term use of heparin-coated equipment for prolonged circulatory support. However, the longest clinical application of a single device is that of an intravascular gas exchanger that remained fully functional during a 29-day implantation period. Finally, it appears, that circulating protamine interacts with surface-bound heparin. Protamine administration should therefore be avoided during perfusion with heparin-bonded equipment to maintain the improved thromboresistance.