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To evaluate the effectiveness and safety of combined epithelium-off cross-linking (CXL) with photorefractive keratectomy (CXL Plus) for correction of the myopic and astigmatic components of keratoconus.Seventy-nine eyes of 46 patients who underwent CXL Plus were enrolled in this retrospective, multicenter, noncomparative clinical study. Uncorrected distance visual acuity, corrected distance visual acuity, refraction, keratometry, and pachymetry measurements were recorded preoperatively and at 3, 6, 12, and 18 months during follow-up.The mean (±SD) preoperative uncorrected distance visual acuity and corrected distance visual acuity were 1.00 ± 0.22 logarithm of the minimum angle of resolution (logMAR) and 0.62 ± 0.38 logMAR, respectively, and improved to 0.71 ± 0.36 logMAR and 0.32 ± 0.18 logMAR postoperatively. The mean k value, mean corneal thickness at the thinnest location, and mean myopic and astigmatic components decreased from 46.58 ± 0.97 D, 473 ± 29 μm, 3.65 ± 1.72 D, and 1.83 ± 0.69 D preoperatively to 43.79 ± 1.17 D, 431 ± 38 μm, 1.02 ± 0.78 D, and 1.15 ± 0.26 D, respectively, during follow-up. Eleven eyes had delayed epithelial healing, 2 had stromal opacities, 1 had primary herpes simplex keratitis, and 5 showed progression of keratoconus.CXL Plus improved the refractive status of keratoconus during 18 months of follow-up, despite its potential early postoperative complications of delayed epithelial healing and corneal haze. CXL Plus reduced the myopic component more than the astigmatic component of keratoconus. However, the safety and stability of the procedure were offset by longer-term postoperative complications and a high rate of postoperative progression of keratoconus.