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Introduction: Hispanic adolescents in the U.S. are disproportionately affected by overweight and obesity compared with their White, non-Hispanic counterparts. This study examines the efficacy of an evidence-based family intervention adapted to target obesity-related outcomes among Hispanic adolescents who were overweight/obese compared with prevention as usual., Study Design: This study was an RCT., Setting/participants: Participants were Hispanic adolescents who were overweight/obese (n=280, mean age=13.01 [SD=0.82] years) in the 7th/8th grade and their primary caregivers. Primary caregivers were majority female legal guardians (88% female, mean age=41.88 [SD=6.50] years)., Intervention: Participants were randomized into the family-level obesity-targeted intervention or referral to community services offered for overweight/obese adolescents and families (condition). Data collection began in 2015., Main Outcome Measures: Primary outcomes included dietary intake (e.g., reduction of sweetened beverages) and past-month moderate-to-vigorous physical activity. Secondary outcomes were BMI and family functioning assessed among adolescents and primary caregivers., Results: Study analyses (2019) indicated no significant intervention effects for adolescents' primary outcomes. Intervention effects were found for parents' intake of fresh fruits and vegetables (β=0.12, 95% CI=0.02, 0.23), added sugar (β= -0.11, 95% CI= -0.22, -0.004), and sweetened beverages (β= -0.12, 95% CI=-0.23, -0.02), and parents showed decreased BMI (β= -0.05, 95% CI= -0.11, -0.01) at 6 months after baseline compared with usual prevention. Intervention effects were found for adolescent family communication (β=0.13, 95% CI=0.02, 0.24), peer monitoring (β=0.12, 95% CI=0.01, 0.23), and parental involvement (β=0.16, 95% CI=0.06, 0.26) at 6 months after baseline compared with prevention as usual., Conclusions: This intervention was not effective in improving overweight/obesity-related outcomes in adolescents. The intervention was effective in improving parents' dietary intake and BMI; however, the effects were not sustained in the long term. Other intervention strategies (e.g., booster sessions, increased nutritional information) may be necessary to sustain beneficial effects and extend effects to adolescent participants., Trial Registration: This study is registered at www.clinicaltrials.gov NCT03943628., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)