Objectives. We examined racial/ethnic differences in significant depressive symptoms among middle-aged women before and after adjustment for socioeconomic, health-related, and psychosocial characteristics. Methods. Racial/ethnic differences in unadjusted and adjusted prevalence of significant depressive symptoms (score ≥16 on the Center for Epidemiologic Studies Depression [CES-D] Scale) were assessed with univariate and multiple logistic regressions. Results. Twenty-four percent of the sample had a CES-D score of 16 or higher. Unadjusted prevalence varied by race/ethnicity (P<.0001). After adjustment for covariates, racial/ethnic differences overall were no longer significant. Conclusions. Hispanic and African American women had the highest odds, and Chinese and Japanese women had the lowest odds, for a CES D score of 16 or higher. This variation is in part because of health-related and psychosocial factors that are linked to socioeconomic status.