OBJECTIVE Extracorporeal life support (ECLS) is a widely accepted modality for the treatment of postoperative low cardiac output syndrome (LCOS) after major cardiac surgery by providing temporary circulatory support for the stunned myocardium. We sought to identify the factors that affect outcomes of ECLS for postoperative LCOS. METHODS From 2005 to 2011, of a total of 9267 adult patients underwent major cardiac surgery, 93 patients (aged, 60.6 ± 13.8 years; 47 women) underwent ECLS to treat postoperative LCOS. RESULTS Thirty-nine (41.9%) patients were weaned off ECLS successfully, and 1 patient underwent heart transplantation. A final total of 23 patients (24.3%), including 1 heart transplantation recipient, survived until the end of the follow-up period (median, 611 days; range, 125-2247 days). On logistic regression analysis, old age (P = .001), a high blood lactate level before ECLS initiation (P < .001), cardiopulmonary bypass weaning failure after surgery (P < .001), and postoperative bleeding (P = .012) were independent factors associated with mortality. In contrast, administration of anticoagulant nafamostat mesilate (P = .040) was found to be associated with improved outcomes of ECLS. When the predictive value of pre-ECLS blood lactate level for mortality was assessed using the receiver operating characteristic curve, the greatest accuracy was obtained at the cutoff value of 7.9 mmol/L, with 63% sensitivity and 68% specificity. CONCLUSIONS High lactate level before ECLS is an independent predictor of mortality after ECLS, necessitating earlier ECLS implementations before profound lactic acidosis develops. Moreover, nafamostat mesilate should be considered as alternative to heparin to reduce the risk of bleeding in these high-risk patients.