OBJECTIVE: To characterize infants aged =90 days enrolled in an international, multicenter, prospective registry of children aged <18 years with acute liver failure (ALF). STUDY DESIGN: The Pediatric Acute Liver Failure (PALF) Study Group collects prospective data on children from birth to 18 years. We analyzed data from infants aged =90 days enrolled in the PALF Study before May 18, 2009. RESULTS: A total of 148 infants were identified in the PALF registry (median age, 18 days). Common etiologies of ALF were indeterminate (38%), neonatal hemochromatosis (13.6%), and herpes simplex virus (12.8%). Spontaneous survival occurred in 60% of the infants, 16% underwent liver transplantation, and 24% died without undergoing liver trsansplantation. Infants with indeterminate ALF were more likely to undergo liver transplantation than those with viral-induced ALF (P = .0002). The cumulative incidence of death without liver transplantation was higher in infants with viral ALF (64%) compared with those with neonatal hemochromatosis (16%) or indeterminate ALF (14%) (P = .0007). CONCLUSION: ALF in young infants presents unique diagnostic considerations. Spontaneous survival is better than previously thought. Liver transplantation provides an additional option for care.