Purpose: To assess the safety and efficacy of photorefractive keratectomy with mitomycin C (PRK-MMC) to correct refractive errors after corneal transplantation. Methods: This was a prospective and noncomparative study of 36 eyes that underwent PRK-MMC after penetrating (n = 34) or lamellar (n = 2) keratoplasty. After mechanical epithelial removal and photoablation, a sponge with mitomycin C 0.02% was applied to the stromal bed for 1 minute. The uncorrected and best-corrected visual acuities, refraction, and complications were assessed. Results: The average follow-up was 16.27 +/- 8.38 months (range, 6-30.5 months). The spherical equivalent decreased from -3.95 +/- 4.11 to -1.07 +/- 1.45 diopters (D) postoperatively (P < 0.001). The mean preoperative astigmatism was 4.42 +/- 1.69 D (range, 1.00-7.25 D); however, surgical correction was limited to 6.00 D. Vector analysis of astigmatic correction showed an index of success of 55%. At the last follow-up, 41.7% (n = 15) and 61.1% (n = 22) of the eyes were within +/- 0.50 and +/- 1.00 D of emmetropia, respectively. Nineteen eyes (52.8%) achieved an uncorrected visual acuity of 20/40 or better. The best-corrected visual acuity remained within 1 line of the preoperative values in 26 cases (72.2%), improved in 8 (22.2%), and decreased in 2 (5.6%). Endothelial cell decompensation was observed in 1 eye (2.8%) 11 months postoperatively, and haze developed in 3 cases (8.3%). Conclusions: PRK-MMC may be an option to correct refractive errors after keratoplasty. A low preoperative endothelial cell count and haze may affect the safety outcomes.