BACKGROUND AND AIM: Major depression is a leading cause of morbidity worldwide, especially during later life. Since heritability is modest (40-50%), there is interest in understanding risk from environmental factors like air pollution. However, research examining this issue is scarce, and often does not use clinical diagnostic criteria. Here, we aimed to quantify associations of air pollution with prevalent major depression in a cohort that deploys diagnostic assessments. METHODS: We conducted a repeated measure analysis of 2008-2016 interviews from the Health and Retirement Study, a nationally representative cohort of older adults in the United States. Major depression status was determined biennially using the Composite International Diagnostic Interview Short Form, with a cutoff of 5. We estimated 1-year average PM2.5, PM10-2.5, NO2, and O3 concentrations at participant residences using fine-scale spatiotemporal models. To estimate prevalence ratios, we fit generalized linear models that accounted for sample weights and clustering by participant. All models included demographic characteristics, individual and neighborhood socioeconomic status, calendar time, and geographic area. RESULTS:Among 25,305 participants with complete data, there was a mean age of 63 years, 53% were female, and most were Non-Hispanic White (73%), with some Black (11%) and Hispanic participants. Eight percent reported major depression. In fully adjusted models, we observed that higher PM2.5 and NO2 concentrations were associated with a greater prevalence of major depression (PR: 1.13 per 3 µg/m³ PM2.5, 95% CI: 1.03, 1.23; PR: 1.23 per 5 ppb NO2, 95% CI: 1.06, 1.20). Only the association with NO2 was robust to adjustment for other pollutants, however, and no associations were observed with PM10-2.5 or O3. CONCLUSIONS:Overall, we observed a robust association of major depression prevalence with long-term exposure to NO2 but not with other air pollutants. This suggests that traffic may be a modifiable risk factor that could be targeted to reduce socioeconomic disparities in mental health. KEYWORDS: Traffic-Related Air Pollution, Major Depression, Psychiatric Epidemiology, Health Disparities