Purpose To investigate the effect of hybrid contact lenses (HCLs) on keratoconus (KCN) progression after accelerated transepithelial cross-linking (A-TE CXL). Methods Thirty-five eyes of 26 patients who preferred Ultrahealth HCLs for an optical correction after A-TE CXL formed the study group, and 45 eyes of 34 patients who preferred spectacle correction were age- and sex-matched to form the control group. Corrected distance visual acuity (CDVA), maximum keratometry, mean keratometry, apical posterior keratometry, cylindrical power, minimum corneal thickness, keratoconus vertex indices and curvature asymmetry indices obtained by Scheimpflug corneal topography were compared before, 6 and 12 months after the procedure. Anterior segment optic coherence tomography (AS-OCT) was performed to measure the apical corneal clearance of HCL-wearing patients. Results The median pre-CXL CDVA value of the patients in the HCL group was logMAR 0.30 (0.20-1.0), and it was logMAR 0.30 (0.10-1.0) in the spectacle-corrected group. There was a significant increase in CDVA 6 and 12 months after CXL procedure in both groups (p < 0.001, 0.003, respectively). The median front curve asymmetry index (FCAsym) significantly improved after A-TE CXL in the HCL group. The pre-CXL and 12th-month topographic comparisons of the spectacle-corrected group revealed no significant difference. In addition, no significant difference was observed between topographic alterations of two groups (p > 0.05). Conclusion The CDVA significantly improved, and KCN progression was halted in patients wearing HCL 12 months after A-TE CXL. Besides, FCAsym indices can be considered for follow-up of the HCL-wearing patients as an assistive parameter to AS-OCT measurements.