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Importance: Alcohol consumption is one of the leading preventable causes of burden of disease worldwide. Selective prevention of alcohol use can be effective in delaying the uptake and reducing harmful use of alcohol during the school years; however, little is known about the durability of these effects across the significant transition from early adolescence into late adolescence and early adulthood., Objective: To examine the sustained effects of a selective personality-targeted alcohol use prevention program on alcohol outcomes among adolescents who report high levels of 1 of 4 personality traits associated with substance use., Design, Setting, and Participants: A cluster randomized clinical trial was conducted to assess the effectiveness of the selective personality-targeted PreVenture program on reducing the growth of risky alcohol use and related harms from early to late adolescence and early adulthood. Participants included grade 8 students attending 14 secondary schools across New South Wales and Victoria, Australia, in 2012 who screened as having high levels of anxiety sensitivity, negative thinking, impulsivity, and/or sensation seeking. Schools were block randomized to either the PreVenture group (7 schools) or the control group (7 schools). The primary end point of the original trial was 2 years post baseline; the present study extends the follow-up period from July 1, 2017, to December 1, 2019, 7 years post baseline. Data were analyzed from July 22, 2021, to August 2, 2022., Interventions: The PreVenture program is a 2-session, personality-targeted intervention designed to upskill adolescents to better cope with their emotions and behaviors., Main Outcomes and Measures: Self-reported monthly binge drinking, alcohol-related harms, and hazardous alcohol use measured by the Alcohol Use Disorders Identification Test-Concise consumption screener., Results: Of 438 participants (249 male [56.8%]; mean [SD] age, 13.4 [0.5] years) from 14 schools, 377 (86.2%) provided follow-up data on at least 2 occasions, and among those eligible, 216 (54.0%) participated in the long-term follow-up. Compared with the control condition, the PreVenture intervention was associated with reduced odds of any alcohol-related harm (odds ratio [OR], 0.81 [95% CI, 0.70-0.94]) and a greater mean reduction in the frequency of alcohol-related harms (β = -0.22 [95% CI, -0.44 to -0.003]) at the 7.0-year follow-up. There were no differences in the odds of monthly binge drinking (OR, 0.80 [95% CI, 0.56-1.13]) or hazardous alcohol use (OR, 0.87 [95% CI, 0.59-1.27]) at the 7.0-year follow-up. Exploratory analyses at the 5.5-year follow-up showed that compared with the control condition, the PreVenture intervention was also associated with reduced odds of monthly binge drinking (OR, 0.87, [95% CI, 0.77-0.99]) and hazardous alcohol use (OR, 0.91 [95% CI, 0.84-0.99]), but this was not sustained., Conclusions and Relevance: This study demonstrated that a brief selective personality-targeted alcohol use prevention intervention delivered in the middle school years can have sustained effects into early adulthood., Trial Registration: anzctr.org.au Identifier: ACTRN12612000026820.