The aim of this study was to assess the long term results of 43 ABO-incompatible liver transplantations performed in 40 patients. The 5-year patient and graft survival rates were 50 and 20%, respectively. In the group of patients transplanted in emergency for fulminant or subfulminant liver failure, ABO incompatibility had no significant impact on patient survival (P = 0.09). Graft survival, however, was significantly impaired (P = 0.0002) through a greater incidence of hyperacute rejection (20%), vascular thrombosis, and biliary injury (56%). Increasing the magnitude of immunosuppression and postoperatively reducing the titer of anti A/B antibodies by plasmapheresis had little influence on the incidence of these complications and were associated with a greater incidence of septic complications. These results indicate that the use of ABO-incompatible liver grafts is a life-saving procedure in patients with life-threatening acute liver failure, but at a high price. Justification for accepting or not accepting an ABO-incompatible graft in these emergency situations depends on the personal choice in giving priority to saving the patient in an acute life-threatening condition or to giving the graft the best chance of success. To avoid this difficult choice, efforts should aim at expanding the pool of grafts available in emergency, at developing artificial support devices that could allow to safely delay transplantation, or at more efficiently controlling the humoral response.