Objective: To describe the ability of the National Eye Institute Visual FunctionQuestionnaire (NEI-VFQ) to detectmeaningful change over time (responsiveness) to the primary Age-Related Eye Disease Study outcomes. Methods: The 25-item NEIVFQ plus appendix was administered at 2 visits at 1-to 4-year intervals to 4119 participants in the Age-Related Eye Disease Study. Events evaluated were progression to advanced age-related macular degeneration (AMD), visual acuity (VA) loss of at least 15 letters, and lens opacity progression. Responsiveness was measured by the t statistic, effect size (ES), responsiveness statistic, and area under the receiver operating characteristic curve. Variance componentswere used to estimate the contributions of events to variability of the NEI-VFQ score. Results: Overall NEI-VFQ score was responsive to AMD progression (t=14.0; P < .001; ES=0.81) andVA(t=16.2; P< .001; ES=0.74). Mean changes ranged from 11 to 25 points for the subscales of general vision, near and distance activities, social functioning, mental health, role difficulties, dependency, and driving. The NEI-VFQ was unresponsive to lens opacity progression, although when the event occurred in the eye with the best vision at the first administration, the lens opacity ES was moderate for the color vision (ES=0.62) and driving subscales (ES=0.66). Progression to advanced AMD and VA loss contributed significantly to the variation in the mean difference in overall VFQ score. Conclusions: Changes in the NEI-VFQ overall and subscale scores of 10 points or more are associated with clinically significant changes in vision and AMD. This finding may assist the design of interventional studies of AMD and VA loss that include the NEI-VFQ as an outcome measure. Objective: To describe the ability of the National Eye Institute Visual FunctionQuestionnaire (NEI-VFQ) to detectmeaningful change over time (responsiveness) to the primary Age-Related Eye Disease Study outcomes. Methods: The 25-item NEIVFQ plus appendix was administered at 2 visits at 1-to 4-year intervals to 4119 participants in the Age-Related Eye Disease Study. Events evaluated were progression to advanced age-related macular degeneration (AMD), visual acuity (VA) loss of at least 15 letters, and lens opacity progression. Responsiveness was was measured by the t statistic, effect size (ES), responsiveness statistic, and area under the receiver operating characteristic curve. Variance components used to estimate the contributions of events to variability of the NEI-VFQ score. Results: Overall Mean changes ranged from 11 to 25 points for the subscales (t = 14.0; P <.001; ES = 0.81) andVA of general vision, near a nd distance activities, social functioning, mental health, role difficulties, dependency, and driving. The NEI-VFQ was unresponsive to lens opacity progression, although when the event was the eye with the best vision at the first administration, the lens opacity ES was moderate for the color vision (ES = 0.62) and driving subscales (ES = 0.66). Progression to advanced AMD and VA loss of increased significantly to the variation in the mean difference in overall VFQ score. Conclusions: Changes in NEI-VFQ overall and subscale scores of 10 points or more are associated with clinically significant changes in vision and AMD. This finding may assist the design of interventional studies of AMD and VA loss that include the NEI-VFQ as an outcome measure.