AIM: To compare the visual results of non-topography-guided and topography-guided photorefractive keratectomy (PRK) applying sequential and simultaneous corneal cross-linking (CXL) treatment for keratoconus. METHODS: Interventional and comparative prospective study. Sixty-nine eyes (36 patients) suffering from keratoconus (stages 1 Amsler-Krumeich classification) were divided into four groups: sequential topography-guided photorefractive keratectomy with CXL, simultaneous topography-guided photorefractive keratectomy with CXL, simultaneous non-topography guided photorefractive keratectomy with CXL, and sequential non-topography guided photorefractive keratectomy with CXL. The main outcome measures were pre- and postoperative uncorrected distance visual acuity (UDVA), best corrected distance visual acuity (CDVA), manifest refraction, contrast sensitivity, and keratometry. RESULTS: All analyzed visual, contrast sensitivity, and refractive parameters showed a significant improvement in the four groups (all P<0.05). A noticeable improvement was seen in keratometry in all the groups, and a remarkable difference was observed between topography-guided groups in comparison to non-topography-guided groups (P<0.05). Interestingly, the improvement in all parameters showed a degree of stability to the end of the follow-up. CONCLUSION: The treatment priorities in all four groups are safety, efficacy, and predictability in the correction of the sphero-cylindrical errors in mild and moderate keratoconus. No significant differences among groups in the recorded objective outcomes were found.