In this study, we report the indications and outcomes of repeat penetrating keratoplasty and the reasons for graft failure. We performed a retrospective data analysis of patients who had undergone 2 or more penetrating keratoplasties for the same eye between 1991 and 2016. Among 1613 penetrating keratoplasties, 149 regrafts of 105 eyes were reviewed. The mean follow-up time after repeat penetrating keratoplasty was 3.2 ± 3.9 (range, 3 months to 17 years) years. The mean number of penetrating keratoplasties was 2.25 ± 0.69 per eye (range, 2-6). The most common primary indication for repeat penetrating keratoplasty was bullous keratopathy (31.4%), which was followed by corneal dystrophy (20.0%). The mean follow-up time was 8.05 ± 5.03 years (range, 8 mo to 24.75 y). At the last follow-up, 62 eyes (59%) had clear grafts and the mean best-corrected visual acuity was 1.26 ± 0.99 (range, 0-3) logMAR. Endothelial failure, especially late endothelial failure (36.9%), and glaucoma-related endothelial failure (18.8%) were the most common reasons for failed grafts. Allograft rejection (17.4%) and graft infection (14.1%) constituted the next most frequent causes. Graft failure is a common indication among penetrating keratoplasties. Primary indications and reasons for failed grafts affect long-term outcomes. Therefore, a better understanding of the indications for risk, leading causes of failed grafts, and complications could help to determine effective preventive measures.