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Purpose: To evaluate 6-year results of standardized epithelium-off corneal collagen cross-linking (CXL) for treatment of progressive corneal ectasia., Design: Prospective, consecutive, interventional case series., Methods: Thirty-six eyes of 25 consecutive patients with documented progressive primary or iatrogenic corneal ectasia underwent CXL following the Siena protocol. The main outcome measures included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, biomicroscopy and fundus appearance, topography-derived steep and flat keratometry (Kmax, Kmin), central corneal thickness (CCT), intraocular pressure with Goldmann applanation tonometer (GAT-IOP), and endothelial cell density (ECD), recorded at baseline and months 1, 3, 6, 12, 24, 36, and 72. Bilateral macular optical coherence tomography was performed at the endpoint visit. The mean follow-up was 66 ± 6 months (range, 60-78 months)., Results: At 6 years, CXL stabilized primary and iatrogenic corneal ectasia in 89% of the patients. In bilateral CXL, the progression of the first eye was highly predictive of the fellow eye's outcome. At the endpoint follow-up, the mean outcome variations were: UDVA: -0.08 ± 0.36 logMAR (P = .2); CDVA: -0.14 ± 0.28 logMAR (P = .004); Kmax: +0.11 ± 1.70 diopters (D) (P = .7); Kmin: -0.25 ± 1.25 D (P = .2); CCT: -16.38 ± 37 μm (P = .01); GAT-IOP: +1.0 ± 2.3 mm Hg (P = .01); ECD: +31 ± 400 cells/mm(2) (P = .6); no cases of macular toxicity or severe adverse events were reported., Conclusions: At 6 years, CXL maintains long-term results in halting the progression of corneal ectasia, with significant improvement in CDVA and long-term stability of keratometry. Further clinical studies with longer follow-up and larger series would be necessary to definitely confirm these results., (Copyright © 2015 Elsevier Inc. All rights reserved.)