Using univariate and multivariate survival analyses, the risk of endothelial rejection (ER) was compared between a group of patients undergoing penetrating keratoplasty (PK) in one eye only (unilateral PK) and a concurrent group who underwent PK in both eyes (bilateral PK). There was no significant difference in the time-related risk of ER between the bilateral and unilateral PK groups, after controlling for the increased risk of ER associated with younger age and preoperative stromal vascularity. Further analysis showed no increased ER risk to the first eye after the second eye's PK in the bilateral PK group. The documentation of simultaneous ER episodes in both eyes of two bilateral PK patients, however, may be evidence of an uncommon sharing of histocompatibility antigen(s) in the donor tissue used in these eyes.