IMPORTANCE: This study provides further evidence from a national sample to generalize the relationship between depression and vision loss to adults across the age spectrum. Better recognition of depression among people reporting reduced ability to perform routine activities of daily living due to vision loss is warranted. OBJECTIVES: To estimate, in a national survey of US adults 20 years of age or older, the prevalence of depression among adults reporting visual function loss and among those with visual acuity impairment. The relationship between depression and vision loss has not been reported in a nationally representative sample of US adults. Previous studies have been limited to specific cohorts and predominantly focused on the older population. DESIGN: The National Health and Nutrition Examination Survey (NHANES) 2005-2008. SETTING: A cross-sectional, nationally representative sample of adults, with prevalence estimates weighted to represent the civilian, noninstitutionalized US population. PARTICIPANTS: A total of 10 480 US adults 20 years of age or older. MAIN OUTCOME MEASURES: Depression, as measured by the 9-item Patient Health Questionnaire depression scale, and vision loss, as measured by visual function using a questionnaire and by visual acuity at examination. RESULTS: In 2005-2008, the estimated crude prevalence of depression (9-item Patient Health Questionnaire score of ≥10) was 11.3% (95% CI, 9.7%-13.2%) among adults with self-reported visual function loss and 4.8% (95% CI, 4.0%-5.7%) among adults without. The estimated prevalence of depression was 10.7% (95% CI, 8.0%-14.3%) among adults with presenting visual acuity impairment (visual acuity worse than 20/40 in the better-seeing eye) compared with 6.8% (95% CI, 5.8%-7.8%) among adults with normal visual acuity. After controlling for age, sex, race/ethnicity, marital status, living alone or not, education, income, employment status, health insurance, body mass index, smoking, binge drinking, general health status, eyesight worry, and major chronic conditions, self-reported visual function loss remained significantly associated with depression (overall odds ratio, 1.9 [95% CI, 1.6-2.3]), whereas the association between presenting visual acuity impairment and depression was no longer statistically significant. CONCLUSIONS AND RELEVANCE: Self-reported visual function loss, rather than loss of visual acuity, is significantly associated with depression. Health professionals should be aware of the risk of depression among persons reporting visual function loss.