AIM: To compare the results of corneal cross-linking (CXL) with isotonic (IR) and hypotonic riboflavin (HR) in patients with keratoconus and to verify the efficacy of keratoconus in thinner corneas. METHODS: Retrospective study of 29 eyes/keratoconus patients submitted to CXL, 15 eyes with application of IR (IR group) and 14 eyes with application of HR (HR group). The parameters analysed included (1-year follow-up): best corrected visual acuity (BCVA), sphere and cylinder, central and finer pachymetry, mean and maximum keratometry (Km and Kmax respectively), complications and progression. RESULTS: An increase on the BCVA scale (logMAR, logarithm of the minimal angle of resolution) was observed in the two groups: 0.26±0.57 (IR) and 0.47±0.72 (HR) before treatment, and 0.13±0.79 (IR) and 0.29±1.52 (HR) at the 1y. Only at 1y, the difference was statistically significant (P=0.018, group IR with higher BCVA). The central pachymetry (μm) decreased at 1mo in both groups, and increased in the following months: 497±28 μm (IR) and 432±14 μm (HR) before treatment, and 480±31 μm (IR) and 424±15 μm (HR) to the 1y. The thinner pachymetry (μm) presented the same evolution: 487±29 μm (IR) and 410±20 μm (HR) before treatment, and 468±33 μm (IR) and 413±13μm (HR) at 1y. Km and Kmax decreased in both groups (P>0.05). Six eyes from each group presented transitory haze. No eye progressed to the 1y. CONCLUSION: The use of hypotonic riboflavin seems to be a valid alternative for performing the traditional corneal cross-linking technique in eyes with a central corneal thickness of <400 μm.