PURPOSE: To report on outcomes after contralateral autologous penetrating keratoplasty (APK). DESIGN: Case series. PATIENT POPULATION: Five patients who received a contralateral APK and a simultaneous allogeneic penetrating keratoplasty in the donor eye at the Bascom Palmer Eye Institute and the Miami Veterans Affairs Hospital. RESULTS: The median patient age at the time of surgery in our 5 patients was 67 years (range, 58-88 years); 4 patients were male and 1 female, and 1 patient was white and 4 were black. The surgery was uneventful in all cases, and no operative or immediate postoperative complications occurred in either eye. Follow-up time ranged from 18 to 54 months (mean, 35 months; median, 34 months). During this time, 4 of the autologous grafts failed because of endothelial attenuation. Identified risk factors for failure in the autologous eyes included the presence of a glaucoma tube (5/5), previous graft failure (4/5), and anterior synechiae (2/5). CONCLUSIONS: This study is the first to describe graft failure because of slow endothelial attenuation after APK. This study underscores the importance of nonimmunologic factors in endothelial cell loss after corneal transplant surgery and highlights the need for further research to understand and modulate endothelial loss.