Purpose: To evaluate the safety and efficacy of corneal collagen cross-linking (CXL) by riboflavin/UV light for the treatment of keratoconus. Methods: This randomized, prospective, and comparative study involved 10 eyes with keratoconus diagnosed between September 2006 and January 2008. Each patient underwent CXL in the keratoconus eye. Preoperative and postoperative (at 1, 3, 6, and 12 months) biomicroscopy examinations, distance uncorrected and best-corrected visual acuities, refractive error, endothelial cell counts, keratometry readings, ultrasound pachymetry, macular thickness, and Scheimpflug analyses were performed and compared. Results: Mean uncorrected visual acuity was 1.18 logarithm of the minimum angle of resolution preoperatively and 0.46 logarithm of the minimum angle of resolution at 12 months postoperatively (P < 0.001). Statistically significant reductions in the mean maximum [2.66 diopter (D), P = 0.04] and minimum (1.61 D, P = 0.03) keratometry values were present at 12 months postoperatively, in addition there was a 2.25 D reduction in the mean spherical equivalent (P = 0.01). At the end of follow-up, 8 (80%) and 6 (60%) of the 10 eyes showed a decrease in the anterior and posterior elevation values, respectively, and the thinnest point of the cornea was statistically thinner by a mean of 13.4 mu m (P = 0.03). No statistically significant differences were found between preoperative and postoperative endothelial cell counts and macular thicknesses. The improvements in visual acuity, keratometry readings, and spherical equivalent values occurred progressively during follow-up. Conclusions: CXL procedure is a safe treatment for keratoconus, yields good visual results, and reduces the progression of the disease, but long follow-up is necessary.