• PURPOSE: To characterize gender differences in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. • DESIGN: Observational, longitudinal study. • METHODS: A total of 1209 subjects at 16 clinics. For eye-specific categorical variables, the number of eyes per subject with the characteristic was counted. For eye-specific continuous variables, the mean of both eyes was calculated. Multivariate linear (for continuous outcomes) and logistic (for categorical outcomes) regression models were created for each baseline characteristic with statistically significant (P ≤ .05) differences between men and women. Age, race, education, and corneal curvature were covariates. • RESULTS: The women were older, more likely to report a family history of keratoconus, more likely to be nonwhite, and less likely to complete college than men. Vogt's striae and monocular and binocular high-contrast entrance acuity were the only visual characteristics that varied between men and women in the multivariate model. Women were more likely than men to report ocular symptoms of dryness and complaints based upon a composite score of ocular symptoms. Women reported more hours per day of near work and were less likely to report the ability to wear contact lenses for enough hours to permit reading at home in the evening. Women reported more visits to their eye care practitioner during the previous 12 months. NEI-VFQ results revealed differences in self-reported difficulty with distance activities and driving. • CONCLUSIONS: Gender differences exist in patient history, vision, and ocular symptoms in keratoconus patients.