ABO-incompatible (ABO-I) liver transplantation is a controversial issue because of the generally less favorable outcome as compared to compatible transplants. Encouraging results have been shown by the introduction of new strategies to reduce posttransplant-specific hemagglutinin (HA) titers with plasmapheresis, reinforced immunosuppression (IS), and the use of splenectomy. We describe a new protocol consisting of daclizumab (DAC) induction, mycophenolate mofetil (MMF)/tacrolimus (TAC)/steroids without splenectomy. Five recipients (mean age of 47 +/- 14 yr) undergoing ABO-I living donor liver transplantation (LDLT) were included in this protocol. Immunoadsorbent columns (Glycosorb ABO) were used for antigen-specific immunoadsorption (ASI). The median follow-up was 18.5 +/- 10.5 months. ASI was very efficient in lowering HA titers (mean log(2) immunoglobulin [Ig] M [IgM] and IgG values before and after ASI were 5.9 +/- 2.8 and 1.2 +/- 1.4 [P= 0.0038] and 6.5 +/- 2.3 and 1.1+/- 1.9, respectively [P= 0.0001]). Persisting low HA titers were observed over time. No sepsis nor cytomegalovirus infection episodes were recorded. Acute cellular rejection (ACR) occurred in 1 recipient responding to steroid pulse therapy. Two grafts were lost in 2 patients due to technical failure during the first postoperative month. We conclude that ASI using Glycosorb ABO, quadruple immunosuppression including DAC and MMF provide high efficiency to lower HA titers over time, avoiding the need for splenectomy. ABO-I LDLT can be performed with this adapted IS protocol.