IMPORTANCE Wavefront-guided (WFG) and wavefront-optimized (WFO) platforms for refractive surgery are designed for improved visual outcomes. It is unclear which treatment profile is superior for patients undergoing photorefractive keratectomy (PRK). OBJECTIVE To compare the safety, efficacy, predictability, stability, and higher-order aberrations in eyes undergoing WFG and WFO PRK. DESIGN, SETTING, AND PARTICIPANTS A prospective, randomized, fellow-eye-controlled clinical trial was conducted at the Byers Eye Institute at Stanford with enrollment between April 2009 and March 2011; 1 year of follow-up was included. Of 90 patients screened, 71 patients (142 eyes) with less than 12.00 diopters (D) of spherical myopia and less than 3.00 D of astigmatism were enrolled consecutively. INTERVENTIONS One eye was randomized to undergo WFG PRK treatment (Visx CustomVue Star S4 IR excimer laser system; Abbott Medical Optics), and the fellow eye received WFO PRK treatment (WaveLight Allegretto Wave Eye-Q 400 Hz excimer laser system; Alcon Surgical). MAIN OUTCOMES AND MEASURES Data on the manifest refraction, uncorrected visual acuity, best-corrected visual acuity, 5% and 25% contrast best-corrected visual acuity, and higher-order aberrations were collected preoperatively and at the 1-, 3-, 6-, and 12-month follow-up visits. RESULTS Eyes undergoing both treatments had improved best-corrected visual acuity