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To investigate the in vivo, corneal, biomechanical changes after corneal collagen cross-linking (CXL) using the Ocular Response Analyzer (ORA) in patients with keratoconus and post-laser in situ keratomileusis (LASIK) ectasia.Single-center, prospective, randomized, controlled, clinical trial. After CXL (69 eyes, 46 keratoconus and 23 post-LASIK), corneal hysteresis (CH) and corneal resistance factor (CRF) were measured using the ORA and analyzed in a treatment, sham control, and fellow eye control group at baseline and 1, 3, 6, and 12 months.There were no significant changes in CH (change = 0.05 ± 1.5; P = 0.78) or CRF (change = 0.29 ± 1.4; P = 0.1) at 1 year compared with preoperative values. Changes in CH and CRF were not correlated with changes in clinical outcomes of uncorrected visual acuity, best spectacle-corrected visual acuity, and maximum keratometry. There were no significant changes in CH in the sham or fellow eye control groups (Psham = 0.7; PFE = 0.3) or CRF (Psham = 0.6; PFE = 0.72).Despite an increase in CRF at one month, there were no statistically significant changes in CH and CRF measurements 1 year after CXL. Development of other in vivo biomechanical metrics would aid in evaluating the corneal response to CXL.