We examined 348 consecutive adult recipients of a corneal transplant for clinical signs of an endothelial rejection episode in a single-center follow-up study. The variables studied included primary diagnosis, number of previous corneal transplants, previous transplant failures from rejection episodes, transplant size, recipient corneal vascularization, donor age, recipient age and sex, past blood transfusions, and number of pregnancies. Five important risk factors were identified: primary diagnosis of herpetic, interstitial, or traumatic keratitis; transplant size 8 mm and larger; more than one previous corneal transplant; recipients younger than 60 years of age; and the presence of recipient corneal vascularization. This information will serve eventually for analyzing the effect of donor recipient tissue matching on corneal transplant rejection.