Objective: To determine factors influencing long-term graft survival and visual acuity in 4834 eyes of 4060 patients receiving their first penetrating corneal graft for keratoconus. Methods: A large cohort study was performed from a national register of corneal grafts in which data were recorded prospectively and analyzed retrospectively. Main outcome measures were graft survival and Snellen visual acuity. Follow-up extended up to 23 years. Results: Kaplan-Meier survival rates of first grafts for keratoconus were 89%, 49%, and 17% at 10, 20, and 23 years, respectively. After 15 years, the graft survival rate was no better than that of all other penetrating grafts (P=.36). Multivariate risk factors influencing failure of first grafts for keratoconus included time to suture removal, postgraft uveitis or microbial keratitis, corneal vascularization prior to or after graft, geographic location of surgery and follow-up (center effect), recipient age at graft, occurrence of rejection episodes, graft size, and surgeon workload. The timing of bilateral grafts made no difference to the risk of rejection. A Snellen visual acuity of 20/40 or better at the most recent follow-up was recorded in 74% of grafts. Conclusions: Penetrating grafts performed for keratoconus exhibited better visual outcome and graft survival than grafts performed for other indications. However, the Kaplan-Meier survival rate of first penetrating grafts for keratoconus was 17% at 23 years after graft and had not plateaued at this time, indicating that young patients are likely to need 1 or more repeated grafts during their lifetime.