To date, only limited cases of Diego blood group disparity in liver transplantation have been reported, and no cases with a long-term clinical course have been documented. Herein, we report a case of Diego blood group disparity in liver transplantation with details of long-term follow-up. The recipient was a 47-year-old woman with primary biliary cirrhosis; her 18-year-old daughter was the donor. Both recipient and donor were of blood type O according to the ABO blood group system. Preoperative serological tests showed the presence of antibodies against the Di(a) antigen only in the recipient, and not in the donor. Thus, the Diego phenotype was Di(a+) in the donor and Di(a-) in the recipient. Living-related liver transplantation was performed in July 2009. Immediate graft function was obtained, and no signs of humoral or cellular rejection were observed during the postoperative period. Further, anti-Di(a) antibodies were not detected throughout the postoperative course. The patient is alive and shows no signs of humoral rejection 34 months after liver transplantation. Liver transplantation has been performed successfully in cases of Diego blood group disparity.