ABO-incompatible (ABO-I) liver transplantation has been performed essentially in patients with acute liver failure awaiting an urgent liver transplantation. Early results with ABO-I liver transplantation were disappointing with a very low graft survival rate (20–50%). The main risk is the occurrence of severe humoral and cellular rejection, vascular thrombosis, and biliary complications. In order to avoid humoral rejection and improve graft survival, total plasma exchange in combination with an intense immunosuppressive regimen has been proposed to decrease hemagglutinin titers in ABO-I liver grafts. In some centers, this regimen was associated with splenectomy, phototherapy, and portal or arterial intrahepatic infusion therapy; however, as these patients are at high risk of sepsis, a selective approach using antigen-specific immunoadsorption with immunoadsorbent columns has been successfully proposed for ABO-I living donor kidney transplantation. Few cases have been reported following liver transplantation. We report our recent experience with three adult patients (two patients with acute liver failure, and one with severe cirrhosis and hepatic encephalopathy) transplanted in an emergency situation with an ABO-I liver graft and managed with the use of GlycoSorb ABO immunoadsorbent columns and a quadruple immunosuppressive regimen with preservation of the spleen. Eight sessions were performed in the three patients. Antigen-specific immunoadsorption greatly lowered the anti-A hemagglutinin titers. None of the three patients developed acute humoral or cellular rejection. Two patients are alive at 1.5 and 3 years follow-up with a normally functioning graft. The third patient died with a functioning graft, one month after the transplantation, from septic complications.