Our objective was to evaluate the effect of ABO antigen blood-group compatibility on corneal allograft rejection. The 199 penetrating keratoplasties performed between 1985 and 1994 were analyzed retrospectively for ABO compatibility and the occurrence of irreversible allograft rejection. Of these, 72 were considered high-risk transplants, as there was significant vascularization of the recipient cornea or a history of irreversible corneal allograft rejection or both. One hundred twenty-seven were low-risk transplants. The data were analyzed by using the Kaplan-Meier method and compared with the log-rank test. Overall, the estimated 1-year graft survival was 83.9% in the low-risk group and 61.4% in the high-risk group (p = 0.001). The estimated 1-year rejection-free graft survival was 89.8% in the low-risk group and 67.1% in the high-risk group (p = 0.0002). In the high-risk group, graft survival (p = 0.008) and rejection-free graft survival (p = 0.0002) were higher in the ABO-compatible subgroup than in the ABO-incompatible subgroup. In the low-risk group, graft survival and rejection-free graft survival of the ABO-compatible and ABO-incompatible subgroups were similar. ABO compatibility may be effective in preventing irreversible allograft rejection in high-risk recipients.