Clinical charts of 80 infants younger than 1 year who presented over a 14-year period (1986 to 2000) with acute liver failure (ALF), defined as prolonged prothrombin time greater than 17 seconds and decrease of clotting factor V plasma level below 50% of normal, were reviewed retrospectively. The main causes of ALF were inherited metabolic disorders in 42.5% of cases, including mitochondrial respiratory chain disorders in 17, type I hereditary tyrosinemia in 12, and urea cycle disorders in 2; neonatal hemochromatosis in 16% of cases; and acute viral hepatitis in 15% of cases (hepatitis B in 6, herpes virus type 6 in 4, and herpes simplex virus type 1 in 2). The cause of ALF remained undetermined in 16% of cases. A total of 19 (24%) infants survived without orthotopic liver transplantation; 38 (47%) infants died from sepsis, multiple organ failure, or because the underlying disease contraindicated orthotopic liver transplantation (12 [15%] infants), and 23 (29%) infants underwent orthotopic liver transplantation within 12 months from onset, 12 of whom are alive with a mean follow-up period of 5.2 years from orthotopic liver transplantation. We conclude that ALF during the first year of life is a severe condition with poor prognosis, despite the advent of liver transplantation.