PURPOSE To compare visual, refractive, topographic, and corneal higher-order aberration outcome at the 2-year follow-up after customized photorefractive keratectomy (PRK) followed by cross-linking (CXL) as a single procedure versus CXL alone in eyes with progressive keratoconus. DESIGN Prospective, interventional, nonrandomized clinical trial. METHODS Seventeen patients (34 eyes) with progressive keratoconus were assigned to 2 groups: the worse eye (17 eyes) was assigned to the PRK plus CXL group and the better eye (17 fellow eyes) was assigned to the CXL group. RESULTS In the PRK plus CXL group, uncorrected distance acuity improved significantly, from a mean ± standard deviation of 0.63 ± 0.36 logarithm of the minimal angle of resolution (logMAR) units to 0.19 ± 0.17 logMAR units (P < .05) and best distance acuity from 0.06 ± 0.08 logMAR to 0.03 ± 0.06 logMAR (P < .05). Manifest refraction spherical equivalent and spherical and cylindrical power improved significantly (P < .05). Simulated keratometry, flattest, steepest, average, cylindrical, apex keratometry, and inferior-superior value decreased significantly (P < .05). Total and coma-like aberrations significantly decreased for all pupil diameters (P < .05). In the CXL group, uncorrected distance acuity improved, but not significantly, from 0.59 ± 0.29 logMAR units to 0.52 ± 0.29 logMAR units, and best distance acuity improved from 0.06 ± 0.11 logMAR units to 0.04 ± 0.07 logMAR units (P > .05). Manifest refraction spherical equivalent and cylindrical power improvement was not significant (P > .05), unlike spherical power (P < .05). Steepest simulated keratometry, average simulated keratometry, and inferior-superior value significantly decreased (P < .05), unlike flattest simulated keratometry, cylindrical simulated keratometry, and apex keratometry (P > .05). Total and coma-like aberrations were not decreased significantly for all pupil diameters (P > .05). No significant endothelial changes were observed in either group. CONCLUSIONS The PRK plus CXL procedure may be a good option to reduce corneal aberrations and stabilize corneas with progressive keratoconus.