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Although the incidence of bleeding complications during extracorporeal membrane oxygenator (ECMO) support has decreased in various trials, bleeding is still the most fatal complication. We investigated the ideal dosage and efficacy of nafamostat mesilate for use with ECMO in patients with acute cardiac or respiratory failure. We assessed 73consecutive patients who received ECMO due to acute cardiac or respiratory failure between January 2006 and December 2009. To evaluate the efficacy of nafamostat mesilate, we divided the patients into 2 groups according to the anticoagulants used during ECMO support. All patients of nafamostat mesilate group were male with a mean age of 49.2 yr. Six, 3, 5, and 3 patients were diagnosed with acute myocardial infarction,cardiac arrest, septic shock, and acute respiratory distress syndrome, respectively. The mean dosage of nafamostat mesilate was 0.64 mg/kg/hr, and the mean duration of ECMO was 270.7 hr. The daily volume of transfused packed red blood cells, fresh frozen plasma,and cryoprecipitate and the number of complications related to hemorrhage and thrombosis was lower in the nafamostat mesilate group than in the heparin group. Nafamostat mesilate should be considered as an alternative anticoagulant to heparin to reduce bleeding complications during ECMO.