The Di antigen in the Diego blood type system is an anthropologic marker of Mongoloids. Here, we report the first case of liver transplantation involving donor/recipient Diego blood type disparity. The recipient was a 58-year-old woman who had developed fulminant hepatic failure, and her 32-year-old daughter was a candidate donor. The recipient and the donor were both ABO blood type O, and were Di (a- b+) and Di (a+ b+), respectively, in the Diego blood system. Living-related liver transplantation was performed, and immediate graft function was obtained. No signs of humoral rejection were observed on postoperative days one to four. Biopsy performed on postoperative days 10, 63, and 87 because of elevation of the serum bilirubin level showed no signs of humoral rejection. In conclusion, liver transplantation can be performed successfully in cases of Diego blood type disparity.