Objectives:To determine short-term outcome for children with acute liver failure (ALF) as it relates to cause,clinical status,and patient demographics and to determine prognostic factors. Study design:A prospective,multicenter case study collecting demographic,clinical,laboratory,and short-term outcome data on children from birth to 18 years with ALF. Patients without encephalopathy were included if the prothrombin time and international normalized ratio remained ≥20 seconds and/or >2,respectively,despite vitamin K. Primary outcome measures 3 weeks after study entry were death,death after transplantation,alive with native liver,and alive with transplanted organ. Results:The cause of ALF in 348 children included acute acetaminophen toxicity (14%),metabolic disease (10%),autoimmune liver disease (6%),non-acetamino- phen drug-related hepatotoxicity (5%),infections (6%),other diagnosed conditions(10%); 49%were indeterminate. Outcome varied between patient sub-groups; 20%with non-acetaminophen ALF died or underwent liver transplantation and never had clinical encephalopathy. Conclusions:Causes of ALF in children differ from in adults. Clinical encephalopathy may not be present in children. The high percentage of indeterminate cases provides an opportunity for investigation. Objectives: To determine short-term outcome for children with acute liver failure (ALF) as it relates to cause, clinical status, and patient demographics and determine prognostic factors. Study design: A prospective, multicenter case study collecting demographic, clinical, laboratory , and short-term outcome data on children from birth to 18 years with ALF. Patients without encephalopathy were included if the prothrombin time and international normalized ratio remained ≥20 seconds and / or> 2, respectively, with vitamin K. Primary outcome measures 3 weeks after study entry were death, death after transplantation, alive with native liver, and alive with transplanted organ. Results: The cause of ALF in 348 children was acute acetaminophen toxicity (14%), metabolic disease (10%), autoimmune liver disease (6%), non-acetamino-phen drug-related hepatotoxicity (5%), infections (6%), other diagnosed conditions (10%); 49% were indeterminate. Outcome varied between patient sub-groups; 20% with non -acetamin ophen ALF died or underwent liver transplantation and never had clinical encephalopathy. Conclusions: Causes of ALF in children differ from in adults. Clinical encephalopathy may not be present in children. The high percentage of indeterminate cases provides an opportunity for investigation.