BACKGROUND: Non-visual factors influence a person's vision-related quality of life (VRQoL). The purpose of this study was to assess the relationship between health literacy and VRQoL in glaucoma patients. METHODS: One hundred and ninety-five subjects with open-angle glaucoma participated in a cross-sectional patient survey and chart review. Subjects were administered a test of health literacy, an assessment of physical and mental well-being, and an assessment of VRQoL, the National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25). Charts were reviewed for visual acuity and visual field results. RESULTS: In univariate analyses, older age (p<0.001), non-White race (p<0.001), worse visual acuity (p<0.001), worse visual field scores (p<0.001), lower level of education (p<0.001), worse health literacy (p<0.001) and worse score on the mental health component of the SF-12 (p = 0.005) were associated with worse VFQ-25 scores. In multivariate analyses, only older age was associated with worse total VFQ-25 scores (p<0.001), although the association between health literacy and the VFQ subscale of dependency remained significant (p = 0.04). CONCLUSIONS: Individuals with a lower health literacy do not appear to have a worse overall VRQoL compared with those with a higher literacy, but worse health literacy is associated with increased dependency.