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Purpose: To compare visual outcomes between wavefront-guided photorefractive keratectomy (PRK) and wavefront-guided laser in situ keratomileusis (LASIK). Setting: Academic center, Salt Lake City, Utah, USA. Methods: In this randomized prospective study, myopic eyes were treated with wavefront-guided PRK and or wavefront-guided LASIK using a Visx Star S4 CustomVue platform with iris registration. Primary outcome measures were uncorrected (UDVA) and corrected (CDVA) distance visual acuities and manifest refraction. Secondary outcome measures were higher-order aberrations (HOAs) and contrast sensitivity. Results: The PRK group comprised 101 eyes and the LASIK group, 102 eyes. At 6 months, the mean UDVA was −0.03 logMAR ± 0.10 [SD] (20/19) and 0.07 ± 0.09 logMAR (20/24), respectively (P = .544). In both groups, 75% eyes achieved a UDVA of 20/20 or better (P = .923); 77% of eyes in the PRK group and 88% in the LASIK group were within ±0.50 diopter of emmetropia (P = .760). There was no statistically significant difference between groups in contrast sensitivity at 3, 6, 12, or 18 cycles per degree. The mean postoperative HOA root mean square was 0.45 ± 0.13 μm in the PRK group and 0.59 ± 0.22 μm in the LASIK group (P = .012), representing an increase factor of 1.22 and 1.74, respectively. Conclusions: Wavefront-guided PRK and wavefront-guided LASIK had similar efficacy, predictability, safety, and contrast sensitivity; however, wavefront-guided PRK induced statistically fewer HOAs than wavefront-guided LASIK at 6 months. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]