Background: Extracorporeal membrane oxygenation (ECMO) provides circulatory support in children with congenital heart disease, particularly in the setting of cardiopulmonary failure and inability to wean from cardiopulmonary bypass. This study summarized the clinical application of ECMO in treatment of heart failure after cardiac surgery in neonates. Methods: Clinical data of 23 neonates who received ECMO support in our center from January 2017 to June 2019 were retrospectively analyzed. Results: Twenty-three neonates, aged from 0 to 25 days and weight between 2300 to 4500 g, with heart failure post-cardiotomy were supported with ECMO. The successful weaning rate was 78.26% and discharge rate was 52.17%. Bleeding and residual malformation were the most common complications. The univariate analysis showed that non-survivors were related to the factors such as higher lactate value of ECMO 12h, 24h (P=0.008, 0.001, respectively), longer time to lactate normalization (P=0.001), lactate>10 mmol/L before ECMO (P=0.01), lower weight (P=0.01), longer ECMO duration (P=0.005), lower platelet count (P=0.001), more surgical site bleeding (P=0.001) and surgical residual malformation (P=0.04). Further logistic regression analysis revealed that higher lactate value of ECMO 24h (P=0.003), longer ECMO duration (P=0.015) and surgical site bleeding (P=0.025) were independent risk factors. Conclusions: ECMO was an effective technology to support the neonates with cardiopulmonary failure after open-heart surgery. Control the lactate acidosis and surgical site bleeding event may be helpful for patients’ recovery.