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To examine the association between neighborhood residence and frailty prevalence in older Mexican Americans (MAs).Cross-sectional, observational study.Socioeconomically and ethnically diverse neighborhoods in San Antonio, Texas.Community-dwelling older MA adults (aged ≥65) who completed the baseline examination of the San Antonio Longitudinal Study of Aging (SALSA) (1992–1996) (N = 394).Subjects were randomly sampled from three types of neighborhoods that varied in ethnic composition and economic environment: barrio (low-income, exclusively MA), transitional (middle-income, equal proportion MAs and European Americans (EAs)) and suburban (upper-income, predominantly EA). Frailty was classified using the Fried criteria. Frailty odds were estimated according to neighborhood using logistic regression, with the suburban neighborhood as the reference category. Covariates included age, sex, diseases, depressive symptoms, and cognitive function.Frailty prevalence was 15.6% in the barrio, 9.4% in the transitional neighborhood, and 3.5% in the suburbs (P = .01). After adjusting for sociodemographic characteristics and disease covariates, odds of frailty were 4.15 times as high for MAs residing in the barrio as for those residing in the suburbs (P = .03). After adjustment for depression and cognition, this association was no longer significant. Diabetes mellitus and depression accounted for the higher odds of frailty in the barrio. Although odds of frailty in the transitional neighborhood were 1.95 times as high as those in the suburbs, the difference was not statistically significant.The ethnic composition and economic environment of the neighborhoods in which MA older adults reside are strongly associated with their odds of being frail.