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To evaluate the effects of medical and surgical therapy for glaucoma in patients requiring repeat penetrating keratoplasty (PK) for endothelial failure.Retrospective review of the charts of all patients undergoing repeat PK at the Cornea Service at Wills Eye Hospital between January 1, 1989 and December 31, 1995. Study end-points were time to first rejection episode, number of rejection episodes, time to endothelial failure, and time to regraft.During the study period, 156 patients underwent repeat PK for irreversible endothelial failure. Ninety-four (60.3%) patients had a concomitant diagnosis of glaucoma. Of these 94, 27 (28.7%) underwent glaucoma surgery. The surgically treated group had a significantly higher percentage of patients with at least one rejection episode (55.6%) than those without glaucoma (32.8%;p = 0.04). Similarly, a significant difference existed in the percentage of both medically and surgically treated glaucoma patients having at least one rejection episode (50%) when compared with patients without glaucoma (32.8%;p = 0.04). Rejection episodes occurred sooner in the glaucoma patients than in the nonglaucoma group (18 months vs. 32 months;p = 0.01), irrespective of glaucoma therapy. Grafts in glaucoma patients failed 12 months earlier than those in patients without glaucoma.In a selected group of patients who required repeat PK for endothelial graft failure, a majority of patients were found to have a history of glaucoma. Among regraft patients, surgical therapy for glaucoma was found to increase the risk of rejection episodes when compared to patients without glaucoma. The patients with glaucoma were found to be at increased risk for early rejection and failure compared to patients without glaucoma.