Purpose: To investigate the outcomes of wavefront-guided photorefractive keratectomy (WG PRK) using prophylactic mitomycin C (MMC) in eyes that had previously undergone radial keratotomy (RK). Design: Retrospective, observational, consecutive case series. Participants: Thirty-two eyes of 27 patients with previous RK that underwent WG PRK with MMC. Methods: The records were reviewed of consecutive RK patients whose eyes underwent WG PRK with MMC in 4 centers with postoperative follow-up of 6 months or longer (range, 6-21 months). Eyes were divided into myopic WG PRK and hyperopic WG PRK groups based on their preoperative spherical equivalent (SE). Preoperative best spectacle-corrected visual acuity (BSCVA) was compared with postoperative uncorrected visual acuity (UCVA) and BSCVA to ascertain efficacy and safety. Change in SE and attempted versus achieved SE were evaluated. Incidences of haze and other complications were recorded. Main Outcome Measures: Uncorrected visual acuity, BSCVA, SE, corneal haze, and other complications. Results: In the myopic WG PRK group (n = 9), UCVA improved by 3 lines on average (P = 0.015) with UCVA of ≥20/20 in 56% and ≥20/40 in 100% of eyes; 55% were within 0.5 diopter (D), and 100% were within 1 D of attempted refraction. In the hyperopic WG PRK group (n = 23), UCVA improved for 3 lines on average (P<0.001), with UCVA of ≥20/20 in 48% and ≥20/40 in 100% of eyes; 57% were within 0.5 D and 74% were within 1 D of attempted refraction. One eye lost 2 lines of BSCVA as a result of the development of mild to moderate haze, but recovered in 4 months. No eyes lost more than 2 lines of BSCVA. Six eyes (19%; 6/32) experienced the development of haze in the postoperative course, with mild to moderate haze in 1 eye and trace haze in the other 5 eyes. No other complications were noted. Conclusions: Wavefront-guided PRK with MMC in eyes with prior RK improved the UCVA significantly and was safe over the short follow-up of this series. Although haze occurred, no eye suffered persistent visual loss of 2 or more lines. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.