To evaluate the safety and clinical outcome of combined non-topography-guided photorefractive keratectomy (PRK) and corneal collagen cross-linking (CXL) for the treatment of mild refractive errors in patients with early stage keratoconus. A retrospective, nonrandomized study of patients with early stage keratoconus (stage 1 or 2) who underwent simultaneous non-topography-guided PRK and CXL. All patients had at least 2 years of follow-up. Data were collected preoperatively and postoperatively at the 6-month, 1-year, and 2-year follow-up visit after combined non-topography-guided PRK and CXL. Seventy-nine patients (140 eyes) were included in the study. Combined non-topography-guided PRK and CXL induced a significant improvement in both visual acuity and refraction. Uncorrected distance visual acuity significantly improved from 0.39 ± 0.22 logMAR before combined non-topography-guided PRK and CXL to 0.12 ± 0.14 logMAR at the last follow-up visit (P <.001) and corrected distance visual acuity remained stable (0.035 ± 0.062 logMAR preoperatively vs 0.036 ± 0.058 logMAR postoperatively, P =.79). The mean spherical equivalent decreased from -1.78 ± 1.43 to -0.42 ± 0.60 diopters (D) (P <.001), and the mean cylinder decreased from 1.47 ± 1.10 to 0.83 ± 0.55 D (P <.001). At the last follow-up visit mean keratometry flat was 43.30 ± 1.75 vs 45.62 ± 1.72 D preoperatively (P = .03) and mean keratometry steep was 44.39 ± 3.14 vs 46.53 ± 2.13 D preoperatively (P = .02). Mean central corneal thickness decreased from 501.74 ± 13.11 to 475.93 ± 12.25 µm following combined non-topography-guided PRK and CXL (P < .001). No intraoperative complications occurred. Four eyes developed mild haze that responded well to a short course of topical steroids. No eye developed infectious keratitis. Combined non-topography-guided PRK and CXL is an effective and safe option for correcting mild refractive error and improving visual acuity in patients with early stable keratoconus.