BACKGROUND Hepatic artery thrombosis (HAT) remains a significant cause of graft failure and mortality after pediatric liver transplantation. Conditions not associated with hepatic failure, such as liver tumors, may be more prone to thrombotic problems after transplant. We hypothesized that liver transplant for hepatic malignancies may be associated with increased rates of HAT in the posttransplant period. METHODS We conducted a retrospective review of pediatric patients (age, 0-21 years) who underwent primary liver transplantation at a free-standing children's hospital from 1990 to 2009. We reviewed cause of underlying liver disease, age, sex, weight, occurrence of HAT, use of antiplatelets and anticoagulants perioperatively, as well as reintervention, retransplant, and death. RESULTS A total of 129 children underwent 146 liver transplants, and 15 (12%) patients developed HAT. Nine liver transplants were performed for hepatic malignancy, and 4 (44%) of these patients developed HAT (relative risk, 4.85; 95% confidence interval, 1.9-12.2; P = .0015). All 4 children with hepatic malignancy and HAT required reintervention, including 3 retransplants (75%). One of these patients died. CONCLUSIONS Hepatic artery thrombosis occurs approximately 5 times more often and appears to be more morbid in children with hepatic malignancy after transplantation. Prospective evaluation of prophylactic anticoagulation regimens in the setting of hepatic malignancy requiring transplantation is warranted.