Acute liver failure (ALF) is an uncommon but potentially lethal drug-related adverse effect that often leads to liver transplantation (LT) or death. A retrospective cohort study was performed with the United Network for Organ Sharing Standard Transplant Analysis and Research files. Recipients who underwent LT for drug-induced acute liver failure (DIALF) from 1987 through 2006 were analyzed. A total of 661 patients transplanted for DIALF were included in the analysis. The 4 leading implicated drug groups were acetaminophen (n Ο 265; 40%), antituberculosis drugs (n Ο 50; 8%), antiepileptics (n Ο 46; 7%), and antibiotics (n Ο 39; 6%). One-year estimated survival probabilities were 76%, 82%, 52%, 82%, and 79% for acetaminophen, antituberculosis drugs, antiepileptics, antibiotics, and others, respectively. The lower rate of survival among those exposed to antiepileptics was observed mainly in children. Of the 22 patients less than 18 years old who had ALF due to antiepileptics, 73% died within the first year. The difference in overall survival between acetaminophen-related and non-acetaminophen-related ALF was not statistically significant. Patients with acetaminophen-related ALF required dialysis prior to LT at a significantly higher rate than all other drug groups (27% versus 3%-10%, P Ο½ 0.0001). According to Cox proportional hazards regression analysis, the independent pretransplant predictors of death after LT were being on life support, DIALF due to antiepileptic drugs at age less than 18, and elevated serum creatinine. In conclusion, the leading drug groups causing LT due to DIALF in the United States were acetaminophen, antituberculosis drugs, antiepileptics, and antibiotics. Children who had ALF due to antiepileptics had a substantially higher risk of death after LT in comparison with other drugs. Patients transplanted for acetaminophen-related ALF required dialysis at a significantly higher rate. Being on life support, DIALF due to antiepileptics (at age less than 18), and elevated serum creatinine were independent pretransplant predictors of poor survival after LT for DIALF.