To investigate the changes in central corneal endothelial cells and corneal thickness in transplanted corneas from 5 to 10 years after grafting. This study also aimed to investigate the development of glaucoma, graft rejection, and graft failure during the first 10 postoperative years. Longitudinal cohort study of 500 consecutive penetrating keratoplasties by 1 surgeon. Patients were asked to return for follow-up examinations at 2 months and at 1, 3, 5, and 10 years after grafting. The authors excluded eyes regrafted during the study and the fellow eyes of bilateral cases, leaving 394 grafts in 394 patients for analysis. Penetrating keratoplasty was performed. Using specular microscopy, the authors measured endothelial cell density, coefficient of variation of cell area, percentage of hexagonal cells, and corneal thickness. The authors performed clinical examinations to determine graft rejection or failure and the development of glaucoma. By 10 years postkeratoplasty, 80 of the 394 patients had died and 68 grafts had failed. Of the remaining 246 patients, 119 (48%) returned for their 10-year examinations. For the 72 patients who returned for all of the scheduled postoperative visits and had no rejection episodes, reoperations, or failure, endothelial cell loss from preoperative donor levels at 10 years was 67 +/- 18% (mean +/- standard deviation), endothelial cell density was 958 +/- 471 cells/mm2, coefficient of variation was 0.32 +/- 0.11, hexagonal cells were 56 +/- 12%, and corneal thickness was 0.58 +/- 0.05 mm. The 5- to 10-year changes for all these values were significant (P < or = 0.004). The mean rate of late endothelial cell loss from 5 to 10 years postkeratoplasty was 4.2% per year. Eyes that were aphakic after grafting had the lowest endothelial cell loss (57 +/- 24%) and the lowest interval cell loss from 5 to 10 years postkeratoplasty (4 +/- 19%). Eyes that were phakic had the highest endothelial cell loss (73 +/- 8%) and 5- to 10-year-interval cell loss (17 +/- 31%). Eyes with posterior chamber lenses had a greater endothelial cell loss (71 +/- 9%) than did eyes with anterior chamber lenses (51 +/- 25%, P = 0.03). The 10-year cumulative risk of glaucoma, rejection, or failure was 21%, 21%, and 22%, respectively. Late endothelial failure became the major cause for graft failure, accounting for 9 of the 11 failures after 5 postoperative years. From 5 to 10 years after penetrating keratoplasty, the annual rate of endothelial cell loss was seven times the normal rate. The endothelial cell loss, pleomorphism, polymegethism, and corneal thickness increased significantly during this time, indicating continued endothelial instability and dysfunction, resulting in an increasing rate of late endothelial failure.