Purpose: Keratoconus is a chronic corneal disease with onset in early adulthood and modest impact on visually acuity. It is not typically considered to have significant public health importance. We evaluated vision-related quality of life (V-QoL) with the NEI Visual Function Questionnaire (VFQ) in patients in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK). Methods: The VFQ measures V-QoL on twelve scales. It was administered to 1,166 CLEK patients at the follow-up examination for seven years. The influence of clinical and demographic factors at baseline was evaluated using GLM. Longitudinal changes were evaluated calculating the slope of the scale score over time, with determinants of a clinically significant decline in scores assessed using logistic regression. A clinically significant change in scale score was defined as 10-points (approximately ½ a standard deviation on most scales). Results: Patients with keratoconus had significantly lower scores on all scales when compared to an age-similar group of people without keratoconus who used a similar method of correction. When compared to people from another study with moderate to advanced macular degeneration (mean age=74) CLEK patients had similar scores on all scales except General Health and Ocular Pain. Mental Health and Role Difficulty scores for patients with keratoconus were similar to those of patients with advanced macular degeneration. The proportion of patients with a 10-point decline in VFQ scores over 7 years ranged from 12% (Color Vision) to 25% (Role Difficulties). In the multivariate model, a decline in visual acuity of five letters (e.g., from 20/20 to 20/25), or an increase in corneal curvature of 2 diopters had the strongest association with a 10-point decline in V-QoL during follow-up. Impaired visual acuity (i.e., best corrected vision worse than 20/40) at baseline was not associated with a significant decline in V-QoL, however corneal curvature >= 52 diopters was associated with a 10-point decline on the Social Function, Dependency, General Vision and Color Vision scales. Conclusions: Traditional clinical measures such as visual acuity do not adequately assess the current or expected impact of keratoconus on a patient's perception of quality of life. It is possible disease onset in early adulthood leads to discordance with health expectations and an impact on social role that results in a perceived disability disproportionate to that measured by clinical indicators.