A prospective study of 84 consecutive patients undergoing penetrating keratoplasty over a 6-month interval was performed to identify risk factors for postoperative epithelial defects. Data collected included donor age, host age, time postmortem until enucleation, general health of donor and host, any history of glaucoma, any surgical procedure, the indication for penetrating keratoplasty, and the presence of any epithelial defect preoperatively in the donor. Patients were evaluated 1 day postoperatively for any epithelial defects greater than 1 mm2 central to the sutures. Single-variable associations and multiple stepwise logistic regression using standard biostatistical techniques were performed. Thirty-one percent (26 of 84) of the patients had epithelial defects on the first postoperative day. Only diabetes in the donor (P = .03) and longer death-to-enucleation times (P = .03) were associated with an increased risk of epithelial defects. We conclude that diabetes in the donor and longer death-to-enucleation times predispose to epithelial defects after penetrating keratoplasty.