SYNOPSISObjectives. This study examined whether the association between obesity and 12-month prevalence of major depressive disorder (MDD) varied according to racial/ethnic status and nativity in representative national samples of black, Latino, Asian, and non-Hispanic white people.Methods. We used data from the Comprehensive Psychiatric Epidemiology Surveys.Results. In analyses by gender, obesity was associated with an elevated risk of MDD among non-Hispanic white women (adjusted odds ratio [AOR] =1.73; 95% confidence interval [CI] 1.27, 2.35; p50.001). Formal test for interaction revealed significant variation by race present between nonHispanic white women and black, Latin, and Asian women. No significant differences were evident among men. In analyses by nativity, the association between obesity and MDD was significant among U.S.-born non-Hispanic white women (AOR51.62; 95% CI 1.16, 2.27; p50.001) and U.S.-born black women (AOR51.29; 95% CI 1.01, 1.66; p50.041). Significant interactions were present among U.S.-born white and black women, Latin women, and Asian women. No significant interactions were evident among foreign-born women. Similarly, no significant differences were present among native-born or foreign-born men.Conclusions. The findings suggest that the association between obesity and MDD varies according to racial/ethnic status and nativity. Understanding the link between obesity and depression may be imperative to designing interventions to address body weight maintenance and reduction strategies among women.