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Purpose: Neighborhood context may influence alcohol use, but effects may be heterogeneous, and prior evidence is threatened by confounding. We leveraged a housing voucher experiment to test whether housing vouchers' effects on alcohol use differed for families of children with and without socioemotional health or socioeconomic vulnerabilities., Trial Design: In the Moving to Opportunity (MTO) study, low-income families in public housing in five US cities were randomized in 1994 to 1998 to receive one of three treatments: (1) a housing voucher redeemable in a low-poverty neighborhood plus housing counseling, (2) a housing voucher without locational restriction, or (3) no voucher (control). Alcohol use was assessed 10 to 15 years later (2008 to 2010) in youth ages 13 to 20, N = 4600, and their mothers, N = 3200., Methods: Using intention-to-treat covariate-adjusted regression models, we interacted MTO treatment with baseline socioemotional health vulnerabilities, testing modifiers of treatment on alcohol use., Results: We found treatment effect modification by socioemotional factors. For youth, MTO voucher treatment, compared with controls, reduced the odds of ever drinking alcohol if youth had behavior problems (OR = 0.26, 95% CI [0.09, 0.72]) or problems at school (OR = 0.46, [0.26, 0.82]). MTO low-poverty treatment (vs. controls) also reduced the number of drinks if their health required special medicine/equipment (OR = 0.50 [0.32, 0.80]). Yet treatment effects were nonsignificant among youth without socioemotional vulnerabilities. Among mothers of children with learning problems, MTO voucher treatment (vs. controls) reduced past-month drinking (OR = 0.69 [0.47, 0.99]), but was harmful otherwise (OR = 1.22 [0.99, 1.45])., Conclusions: For low-income adolescents with special needs/socioemotional problems, housing vouchers protect against alcohol use., (© 2022 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcoholism.)