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To assess the effects of corneal collagen cross-linking (CXL) on contrast sensitivity (CS), visual acuity, and corneal topography investigating possible predictors of efficacy.Sixty-eight eyes of 34 patients with progressive keratoconus were enrolled in this prospective study. CXL was performed in one eye and the other eye was left untreated as a control. CS, best spectacle–corrected visual acuity (BSCVA), simulated keratometry in the steepest meridian (SimK-s), mean power in the central 3-mm zone (C-MP), mean power in the paracentral 3- to 5-mm zone (P-MP), maximum keratometric power in the central zone (C-Kmax), and maximum keratometric power in the paracentral zone (P-Kmax) were evaluated at baseline, 40 days, 3 months, 6 months, 1 year, and after 2 years of follow-up.Treated eyes showed an improvement (P < 0.001) of +0.16 logCS and −0.16 logarithm of the minimum angle of resolution (logMAR) and a reduction in SimK-s of −0.61 diopter (D), C-Kmax −1.11 D, P-Kmax −0.99 D, C-MP −0.39 D, and P-MP −0.30 D. Of the treated eyes, 43.3% had a decrease in C-Kmax greater than 1 D, 50% by 0 to 0.99 D, and 6.7% had an increase of up to +0.89 D. Treated eyes with keratometric apex in the central 3-mm zone (CKA) improved BSCVA −0.19 logMAR and CS +0.19 logCS; whereas in treated eyes with paracentral keratometric apex (PKA), the improvement was −0.13 logMAR and +0.16 logCS.CXL with riboflavin and UV-A improved CS and inhibited the progression of keratoconus. As a predictor of treatment efficacy, eyes with CKA showed greater improvement in BSCVA after CXL when compared with eyes with PKA.