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PURPOSE To evaluate the clinical results of epitheliumoff corneal cross-linking (CXL) during a 7-year follow-up. METHODS This retrospective, non-randomized, single-center interventional study enrolled 34 consecutive eyes of 24 patients with progressive keratoconus undergoing CXL surgery with epithelium removal. Visual, refractive, corneal topographic, pachymetric, and anterior segment changes were evaluated at 1, 3, and 7 years after surgery. RESULTS Significant reduction of refraction was observed at 1 year postoperatively (P ≤ .006), with an additional significant reduction between the 1- and 3-year postoperative visits (P ≤ .002) and no significant changes afterward (P ≥ .156). Regarding corrected distance visual acuity (CDVA), a significant improvement was detected at 1 year after surgery (P < .001), with an additional improvement between 1 and 3 years postoperatively (P = .001), and no significant changes at the end of the follow-up (P = .518). Significant corneal flattening was observed at 1, 3, and 7 years after surgery (P ≤ .041). Likewise, a significant central thinning was observed at 1 year postoperatively (P < .001), with no significant changes afterward (P ≥ .112). Anterior maximum elevation only changed significantly between 1 and 3 years after surgery (P = .002), whereas the posterior maximum elevation changed significantly at all time points of the follow-up (P ≤ .034). No significant changes with surgery in anterior segment volume (P ≥ .377) and anterior chamber depth (P ≥ .142) were detected. CONCLUSIONS The effect of epithelium-off CXL in progressive keratoconus is maintained 7 years after surgery. Long-term corneal changes after this procedure may be influenced by an age-related corneal stiffening process. [J Refract Surg. 2018;34(3):181-186.].