Purpose Keratoconus is a chronic, noninflammatory disease of the cornea with onset in early adulthood. As these years are important to financial and social health, keratoconus may have more severe impact on quality of life than would be expected given its clinical severity. We examined the vision-related quality of life of patients in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Design Cross-sectional study. Methods The National Eye Institute-Visual Function Questionnaire (NEI-VFQ) was administered to 1166 CLEK Study patients at their first annual follow-up examination. Associations between clinical and demographic factors and NEI-VFQ scale scores were evaluated. Results Binocular entrance visual acuity worse than 20/40 was associated with lower quality of life scores on all scales except General Health and Ocular Pain. A steep keratometric reading (average of both eyes) >52 diopters (D) was associated with lower scores on the Mental Health, Role Difficulty, Driving, Dependency, and Ocular Pain scales. Scores for CLEK patients on all scales were between patients with category 3 and category 4 age-related macular degeneration (AMD) except General Health, which was better than AMD patients, and Ocular Pain, which was worse than AMD patients. Conclusions Keratoconus is a disease of relatively low prevalence that rarely results in blindness, but because it affects young adults, the magnitude of its public health impact is disproportionate to its prevalence and clinical severity.