PURPOSE: To determine if National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores decrease with worsening visual acuity (VA) in American Indian/Alaska Natives (Al/AN), as well as determine the other associated explanatory factors for vision-related quality of life. METHODS: The study included 414 randomly selected AI/AN tribal members aged 40 years or older from the Pacific Northwest. We excluded candidates who were deceased, seriously ill, had dementia, or otherwise were unable to perform subjective testing such as visual field testing. The participants completed the NEI-VFQ-25, as well as a detailed eye examination. We defined visual impairment as presenting distance VA 20/40 or worse in the better-seeing eye. The main outcome measures were NEI-VFQ-25 composite and subscale scores. We compared median NEI-VFQ-25 composite and subscale scores in those with visual impairment to those without visual impairment. RESULTS: Visual impairment occurred in 53 (12.8%, Cl: 9.6-16.0) participants. The NEI-VFQ-25 median composite score was significantly lower in those with visual impairment as compared to those without visual impairment (77.5 vs. 90.1, p = .001). A univariate analysis showed VA to be significantly (p