OBJECTIVES: Depressive and anxiety disorders are the most common mental disorders and often lead to costly mental distress in the US. The aim of this study was to determine if there are variations in the geographic distribution of self-reported lifetime depression using data from the 2012 Behavior Risk Factor Surveillance System (BRFSS). METHODS: Data were from the 2012 BRFSS, a cross-sectional random-digit-dialed telephone survey of 475,687 noninstitutionalized adult population aged 18 years or older. The outcome variable was self-reported depression and the independent variable was geographic region as defined by the US Census Bureau (Midwest, Northeast, South, and West). A logistic regression model was constructed to examine the association between geographic region and socio-demographic factors and depression. RESULTS: There was a significant relationship between geographic region and lifetime depression in the bivariate analysis (p < 0.0001). After adjusting for the effects of other variables, geographic region was not significantly associated with lifetime depression. However, there was a significant relationship between geographic region and race in a bivariate analysis (p < 0.0001). Therefore, race was removed from the multivariate model. Thereafter, geographic region became significantly associated with lifetime depression (p < 0.0001). Participants living in the West and Northeast regions were 1.14 (95% CI, 1.06 – 1.18) and 1.11 (95% CI, 1.05 – 1.18) more likely to report lifetime depression compared to participants living in the South. The Midwest region was not significantly associated with lifetime depression. CONCLUSIONS: There was no association between lifetime depression and geographic region with race in the model, but the association became significant after removing race. Because removing race resulted in a significant association, racial distribution may be more indicative of lifetime depression than geographic region. Public health services should consider the racial distribution of a geographic region when addressing the burden of lifetime depression.