Purpose To develop a vision-targeted health-related quality of life (HRQOL) measure for the NIH Toolbox for the Assessment of Neurological and Behavioral Function. Methods We conducted a review of existing visiontargeted HRQOL surveys and identified color vision, low luminance vision, distance vision, general vision, near vision, ocular symptoms, psychosocial well-being, and role performance domains. Items in existing survey instruments were sorted into these domains. We selected non-redundant items and revised them to improve clarity and to limit the number of different response options. We conducted 10 cognitive interviews to evaluate the items. Finally, we revised the items and administered them to 819 individuals to calibrate the items and estimate the measure's reliability and validity. Results The field test provided support for the 53-item visiontargeted HRQOL measure encompassing 6 domains: color vision, distance vision, near vision, ocular symptoms, psychosocial well-being, and role performance. The domain scores had high levels of reliability (coefficient alphas ranged from 0.848 to 0.940). Validity was supported by high correlations between National Eye Institute Visual Function Questionnaire scales and the new-vision-targeted scales (highest values were 0.771 between psychosocial well-being and mental health, and 0.729 between role performance and role difficulties), and by lower mean scores in those groups self-reporting eye disease (F statistic with p<0.01 for all comparisons except cataract with ocular symptoms, psychosocial well-being, and role performance scales). Conclusions This vision-targeted HRQOL measure provides a basis for comprehensive assessment of the impact of eye diseases and treatments on daily functioning and well-being in adults. © Springer Science+Business Media Dordrecht 2013.