Survival in ABO-incompatible (ABO-I) liver transplantation has been reported to be between 40% and 60%. Management techniques have included routine immunosuppression as well as prophylactic antilymphoblast globulin, pre- and posttransplant plasmapheresis (PLPH), and splenectomy. Over a 6-year period, 155 orthotopic liver transplants were performed in 139 pediatric patients. Seven children received an ABO-I allograft. In the latter transplants, immunosuppression consisted of triple-drug therapy (cydosporine A, prednisone, and azathioprine) along with prospective double-volume PLPH for ABO titers (IgA and IgM) ≥ 1:8. Splenectomy was not performed on any patient. One patient was refractory to PLPH and was treated with a hemofiltration system using an immunoadsorption cartridge with synthetic A group antigen. The overall survival for patients receiving ABO-I allografts was 57% (4/7), with a 67% (4/6) graft survival in those patients treated with PLPH. The graft survival for patients treated with prospective PLPH and MALG was 60% (3/5). There was a 60% incidence of rejection in those patients treated with prospective PLPH and these episodes were all mild (steroid bolus only). While ABO-I transplantation is a reasonable option in the emergency setting, further study is necessary before it should be routinely used to increase the general donor organ pool in pediatric liver transplantation.