Aim and objective: To evaluate the 3-year follow-up clinical outcomes obtained in corneal ectasia using Epi-ON corneal collagen cross-linking (CXL). Materials and methods:This study is a retrospective study enrolling 46 eyes from 32 patients with progressive corneal ectasia and treated with Epi-ON CXL in the period from September 2012 to April 2016. Two groups were differentiated according to the type of corneal ectasia: ectasia post-LASIK group (EPL, 12 eyes) and primary ectasia group (34 eyes). Two different platforms were used for the surgical protocol: VEGA CBM X LINKER platform (CSO, Firenze, Italy) and KXL (Avedro, Waltham, Massachusetts, USA). Visual, refractive, and corneal tomographic outcomes were evaluated during a 3-year follow-up. Results: A statistically significant improvement in the logMAR corrected distance visual acuity (CDVA) was observed in the whole sample (p <0.001) during the follow-up, with half of the sample improving one or more lines of CDVA. Likewise, only significant changes were detected in steepest keratometry (p <0.001), corneal astigmatism (p = 0.012), and index of height asymmetry (p = 0.021), with a trend to increase. Regarding the comparison between groups, more significant improvement in CDVA was found in the EPL group compared to the primary ectasia group (−0.07 ± 0.09 vs −0.15 ± 0.14, p = 0.028). Likewise, a significant trend to more corneal thinning was observed in primary ectasia group (p = 0.034). Conclusion:Epi-ON CXL is efficacious for stabilizing the progression of primary and iatrogenic ectasias for most cases, with significant improvement of visual acuity associated.