BACKGROUND Extracorporeal membrane oxygenation (ECMO) is widely used for postcardiotomy cardiogenic shock in children. However, the efficacy of ECMO for early post-heart transplant graft failure in infants has not been reported. Our aims were to determine: (1) the utility of ECMO in infants with severe donor-heart dysfunction, (2) predictors for requiring ECMO, and (3) the long-term outcome of surviving ECMO patients. METHODS All infants (age < 6 months at listing) undergoing heart transplantation were reviewed. Diagnostic categories were hypoplastic left heart syndrome (HLHS) and non-HLHS (complex congenital heart disease and cardiomyopathies). Continuous and categorical comparisons were by Wilcoxon's rank sum test and Fisher's exact test respectively. RESULTS 14 (12 HLHS, 2 non-HLHS) of 63 (46 HLHS, 17 non-HLHS) infants were placed on ECMO. Ten patients (71%) were successfully weaned from ECMO and 8 (57%) were discharged alive. All ECMO hospital survivors remain alive (mean follow-up 36.2 +/- 21.4 months, range 13.1-77.6 months). Mean duration of ECMO support was 68 hours in weaned patients vs 144 hours (p = 0.19) in nonweaned patients, and 64 hours in survivors vs 123 hours (p = 0.35) in nonsurvivors. ECMO deaths were due to sepsis (n = 3), intractable pulmonary hypertension (n = 2), and intracranial bleed (n = 1). Neurologic deficits occurred in 2 survivors. Median ICU and hospital stays for ECMO survivors were 29 and 33 days vs 7 (p = 0.0003) and 9 (p = 0.0004) days for non-ECMO patients. Age listed, age transplanted, wait time, body weight, donor/recipient weight ratio, total ischemia time, and diagnosis did not predict the need for ECMO. CONCLUSIONS (1) ECMO is useful for post-heart transplant circulatory support in infants with early graft failure. (2) All survivors were weaned in fewer than 4 days. (3) Three-year survival of ECMO hospital survivors has been high, but neurologic complications are prevalent.