OBJECTIVES: The purpose of the current study was to assess our multidisciplinary approach consisting of early application of neurology-oriented intensive care, aggressive artificial liver support and liver transplantation at the appropriate time for infants with acute liver failure. DESIGN: Retrospective cohort study. SETTING: A tertiary pediatric medical center in Japan. PATIENTS: Seventeen infants younger than 12 months with acute liver failure who subsequently underwent liver transplantation between February 2006 and June 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The patients varied from 1 to 11 months, with a median of 6 months. The median body weight was 8.0 kg (range, 2.7-10 kg). With respect to the encephalopathy grading before liver transplantation, four cases were categorized as grade II, seven cases were categorized as grade III, and five cases were categorized as grade IV. Continuous veno-venous hemodiafiltration and plasma exchange were applied to all the infants until liver transplantation. Bilirubin, ammonia, prothrombin time/international normalized ratio and creatinine decreased significantly after continuous veno-venous hemodiafiltration + plasma exchange (p < 0.001). The median value of catecholamine index changed from 10 to 0 (range, 0-20.6). Notably, among the 16 infants who underwent electroencephalography assessment, five did not show slow waves throughout their stay, and one who did so before treatment ceased to show any after treatment. The all patients underwent living-donor liver transplantation and were subsequently discharged from the PICU. The overall survival rate was 88% (15/17) with a median follow-up period of 28 months (range, 2-64 mo). Regarding the neurological outcomes of the survivors, 73% (11/15) had no neurological morbidities and 20% (3/15) had mild disabilities. CONCLUSIONS: Our multidisciplinary approach for infants with acute liver failure achieved favorable outcomes. Further investigations are needed to examine the efficacy of the artificial liver support.