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Purpose: To determine the changes in corneal thickness over time after corneal collagen crosslinking (CXL) for keratoconus and corneal ectasia. Setting: Cornea and refractive surgery subspecialty practice. Design: Prospective randomized controlled clinical trial. Methods: Corneal thickness at the apex, thinnest point, and pupil center were measured using Scheimpflug imaging (Pentacam) at baseline and 1, 3, 6, and 12 months after CXL. The treatment group was compared with both a sham-procedure control group and a fellow-eye control group. Associations with clinical outcomes (uncorrected and corrected distance visual acuities and maximum keratometry) were analyzed. Results: The study comprised 82 eyes, 54 with keratoconus and 28 with ectasia after laser in situ keratomileusis. The mean preoperative thinnest pachymetry was 440.7 μm ± 52.9 (SD). After CXL, the cornea thinned at 1 month (mean change −23.8 ± 28.7 μm; P<.001) and from 1 to 3 months (mean change −7.2 ± 20.1 μm, P=.002), followed by a recovery of the corneal thickness between 3 months and 6 months (mean +20.5 ± 20.4 μm; P<.001). At 1 year, apex and pupil-center thicknesses returned to baseline (P=.11 and P=.06, respectively); however, the thinnest pachymetry remained slightly decreased from baseline to 12 months (mean change −6.6 ± 22.4 μm; P=.01). The recovery of corneal thickness was more rapid in ectasia than in keratoconus. There was no association between the degree of corneal thinning at 3 months and clinical outcomes after CXL. Conclusions: After CXL, the cornea thins and then recovers toward baseline thickness. The cause and implications of corneal thickness changes after CXL remain to be elucidated. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes. [ABSTRACT FROM AUTHOR]