Hemolysis may occur after organ transplantation. In most cases, hemolysis is drug-related, such as to cyclosporin, etc. However, it is important to consider graft-versus-host antibody formation as one of the causes of hemolysis. We evaluated the effect of local graft irradiation as a method of preventing hemolysis arising from ABO antibody formation after ABO-mismatched renal transplantations. The participants in this study were 44 patients who had undergone ABO-mismatched renal transplantation. Of these patients, 23 were subjected to postoperative local irradiation, and 21 were not. We examined the characteristics of anti-blood-type antibodies, and we also compared the frequency of the development of antibody formation and hemolysis development between the groups. The development rates of anti-ABO-antibody formation and hemolysis were significantly higher in the patients without local irradiation (15/21, 71%; 6/21, 29%) than in those with local irradiation (1/23, 4%; 0/23, 0%). The elevated antibodies mainly belonged to the IgG class, not the IgM class. The hemolysis- and antibody formation observed in the patients originally without postoperative local irradiation was dramatically improved by graft irradiation. Local graft irradiation after ABO-mismatched renal transplantations may be needed to prevent the formation of anti-ABO antibodies and to impede the development of hemolysis.