Since the inception of extracorporeal membrane oxygenation (ECMO), hemorrhage has been a major complication often limiting its usefulness. This study was undertaken to evaluate the effect of aminocaproic acid (AMICAR), an inhibitor of fibrinolysis, on all hemorrhagic complications of ECMO including intracranial hemorrhage (ICH). In 1990, 49 neonates and 5 older children received ECMO therapy. None of these patients received AMICAR. In 1991, 51 neonates and 5 older children received ECMO. Forty-two of these patients who were considered to be at high risk for bleeding complications (preexisting or anticipated surgical procedures, preexisting ICH, or profound hypoxia, acidosis, coagulopathy, or prematurity) were given AMICAR. The remaining 14 low-risk neonates did not receive AMICAR, and for purposes of analysis were combined with the 1990 group. AMICAR was administered just prior to or after cannulation (100 mg/kg, intravenously) and was infused continuously at 30 mg/kg/h until decannulation. Except for the addition of AMICAR, the ECMO protocol was identical for these two patient groups. Patients who received AMICAR had significantly less bleeding while on ECMO (P = .03) and required fewer blood transfusions (P = .01) than patients not receiving AMICAR. This difference was most significant in the congenital diaphragmatic hernia and cardiac subgroups (P = .0001) and was not significant in the meconium aspiration subgroup (P = .1). The incidence of ICH in the neonatal subgroup was also significantly reduced with no patient on AMICAR developing a new or extending a preexisting ICH (P = .007). Reexploration of the cannulation site for bleeding was also reduced in the AMICAR-treated group but the difference failed to reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)