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To report a case of severe corneal endothelial damage after collagen cross-linking treatment in a 37-year-old man with progressive keratoconus with a corneal thickness of more than 400 μm.After central epithelial debridement, the left cornea was cross-linked for 25 minutes using dextran–riboflavin solution and UV-A light of 370 nm with an irradiance of 3.0 mW/cm2. One month after cross-linking treatment, the patient presented with massive corneal edema. He was treated with 1% prednisolone and carboxymethylcellulose 1% eyedrops 4 times a day for 3 months. Specular microscopy with endothelial cell counting was performed after resolution of the corneal edema 6 months after cross-linking.Despite intense treatment, a ring-shaped corneal scar remained, and uncorrected visual acuity was finger counting. Cell density after resolution was 1776 cells per square millimeter in the affected eye compared with 2978 cells per square millimeter in the untreated fellow eye.Corneal thickness is not the only factor for corneal endothelial damage after cross-linking procedure.