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Purpose: To determine intraoperative changes in corneal thickness and outcomes of corneal collagen crosslinking (CXL) using 2 intraoperative regimens: riboflavin-dextran or hypotonic riboflavin., Setting: Cornea and refractive surgery practice, Teaneck, New Jersey, USA., Design: Prospective randomized case series., Methods: Eyes with keratoconus or corneal ectasia were treated. All eyes received preloading with riboflavin 0.1% in 20% dextran. During ultraviolet-A (UVA) exposure, patients were randomly assigned to 1 of 2 study arms; that is, riboflavin-dextran or hypotonic riboflavin. Intraoperative pachymetry was measured before and after the corneal epithelium was removed, after initial riboflavin loading, and after UVA light exposure. Patients were evaluated for maximum keratometry (K), uncorrected distance visual acuity (UDVA), corrected distance visual acuity, corneal thickness, and endothelial cell count (ECC)., Results: Forty-eight eyes were treated. After removal of the epithelium and riboflavin loading, the mean pachymetry was 430 μm and 432 μm in the standard group and hypotonic group, respectively. Immediately after 30-minute UVA administration, the mean pachymetry was 302 μm and 342 μm, respectively. There was no statistically significant difference in the postoperative maximum K change, UDVA, corneal thickness, or ECC between the 2 groups., Conclusions: The cornea thinned substantially during the CXL procedure. The use of hypotonic riboflavin rather than riboflavin-dextran during UVA administration decreased the amount of corneal thinning during the procedure by 30%, from 128 μm to 90 μm. However, there were no significant differences in clinical efficacy or changes in ECC or function between groups postoperatively. In general, corneal thinning during CXL did not seem to compromise the safety of the endothelium., Financial Disclosures: Dr. Hersh is a consultant to Avedro, Inc. Dr. Rosenblat has no financial or proprietary interest in any material or method mentioned., (Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)