OBJECTIVE To compare the longitudinal changes in corneal endothelial cell density (ECD) and the incidence of postoperative complications between eyes with endothelial decompensation after repeat penetrating keratoplasty (RPK) and those after primary penetrating keratoplasty (PPK). METHODS Fifty-seven eyes with endothelial decompensation scheduled for RPK (RPK group) and 57 eyes with endothelial decompensation scheduled for PPK (PPK group) were enrolled. Corneal ECD was evaluated using a specular microscope at 1, 3, 6, 9, and 12 months, and every 6 months until 60 months postoperatively. Visual acuity (VA) and incidence of graft failure, graft rejection, or marked increase in intraocular pressure were examined. RESULTS Corneal ECD decreased gradually and percentage of cell loss at 60 months was approximately 73% in both groups; these did not differ significantly between groups throughout the follow-up (P ≥ 0.2209). The incidence of graft failure (52.6% in the RPK group and 36.8% in the PPK group), immune rejection, and marked increase in intraocular pressure did not differ significantly between groups (P ≥ 0.0898), although corrected VA was worse in the RPK group. The most common cause of graft failure in both groups was late endothelial failure. The outcomes were not significantly different between eyes that underwent a first RPK and those that underwent a second or subsequent RPK. CONCLUSIONS Corneal endothelial cell loss and complications are comparable between eyes with endothelial decompensation after RPK and those after PPK, although VA is worse in eyes after RPK. The outcomes after a first RPK did not differ from those after multiple RPKs.