AIM: To evaluate the visual outcomes of simultaneous non-topography guided photorefractive keratectomy (PRK) and corneal collagen cross-linking (CXL) in eyes with keratoconus 5y after the procedure. METHODS: Prospective, interventional, non-randomized, and non-controlled case series design was used. Sixty eyes of 30 patients (16 males and 14 females; age: 21-41y) with mild, non-progressive (stages 1-2) keratoconus were enrolled. Refraction, uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) , flat and steep keratometry readings, and adverse events were evaluated preoperatively and postoperatively. Data were collected preoperatively and postoperatively at 3mo, 1, 2, 3, 4, and 5y follow-up visits after combined non-topography-guided PRK with CXL was performed. All patients had at least 5y of follow-up. RESULTS: All study parameters showed a statistically significant improvement at 5y over baseline values. The mean follow-up time was 68.20±4.71mo (range: 60-106mo). Patients showed a significant improvement in UDVA from 1.24±0.79 logMAR prior to combined non-TG-PRK+CXL to 0.06±0.15 logMAR postoperatively at the time of their last follow-up visit. CDVA significantly increased from 0.06±0.19 logMAR preoperatively to 0.03±0.12 logMAR postoperatively. A significant decrease in the mean spherical equivalent (SE) refraction was observed from -2.28±1.8 to -0.79±0.93 diopters (D) (P<0.05), and the manifest sphere decreased from -1.62±1.23 to -0.27±0.21 D (P=0.001). The manifest cylinder significantly decreased from -1.73±0.86 to -0.29±0.34 D postoperatively (P=0.001). The mean steep keratometry was 45.13±1.32 vs 47.28±2.12 D preoperatively (P<0.05), and the preoperative mean steepest keratometry (Kmax) 48.6±3.1 was reduced significantly to 46.8±2.9 postoperatively (P<0.05). CONCLUSION: Combined non-TG-PRK with 15min CXL is an effective and safe option for correcting mild refractive error and improving visual acuity in patients with mild stable keratoconus.