PROJECT SUMMARY/ABSTRACT Life support with extracorporeal circulation through a membrane oxygenator (ECMO) is a mainstay of advanced critical care. However, clotting in the ECMO circuit and bleeding from the patient are the major complications, accounting for morbidity and mortality in 30% of patients. Surface–based coatings are available, but still require systemic anticoagulation because these surfaces do not prevent platelet adhesion and activation. We have developed a nonthrombogenic surface which prevents platelet activation at the surface. This could eliminate the need for systemic anticoagulation and prevent major bleeding and circuit clotting complications. The surface is based on nitric oxide (NO), which is the mechanism of surface anticoagulation of the normal endothelium. The chemistry, coating, NO generation, and effectiveness have been tested in preliminary studies. This research will refine the nitric oxide surface anticoagulation system (NOSA), and demonstrate effectiveness compared to systemic anticoagulation. The results will apply to nonthrombogenic surfaces for other extracorporeal devices such as hemodialysis, hemofiltration, and cardiopulmonary bypass.