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This study evaluated the efficacy of the selective personality-targeted PreVenture program in reducing cannabis and stimulant use over a 7-year period spanning adolescence and early adulthood. A cluster randomized controlled trial was conducted in 14 Australian schools. Schools were randomized to PreVenture, a brief personality-targeted selective intervention, comprising two 90-minute facilitator-led sessions delivered one week apart, or a control group (health education as usual). Only students who scored highly on one of four personality traits (anxiety sensitivity, negative thinking, impulsivity, sensation seeking) were included. Students completed online self-report questionnaires between 2012 and 2019: at baseline; post-intervention; 1-, 2-, 3-, 5.5- and 7-years post-baseline. Outcomes were past 6-months cannabis use, stimulant use (MDMA, methamphetamine or amphetamine) and cannabis-related harms. The sample comprised 438 adolescents (M age =13.4 years; SD=0.47) at baseline. Retention ranged from 51% to 79% over the 7-years. Compared to controls, the PreVenture group had significantly reduced odds of annual cannabis-related harms (OR=0.78, 95% CI=0.65–0.92). However, there were no significant group differences in the growth of cannabis use (OR=0.84, 95% CI=0.69–1.02) or stimulant use (OR=1.07, 95% CI=0.91–1.25) over the 7-year period. PreVenture was effective in slowing the growth of cannabis-related harms over time, however owing to missing data over the 7-year trial, replication trials may be warranted to better understand the impact of the PreVenture intervention on cannabis and stimulant use among young Australians. Alternative implementation strategies, such as delivering the intervention in later adolescence and/or providing booster sessions, may be beneficial. • One of the longest follow-up studies of a substance use prevention program globally. • PreVenture reduced cannabis-related harms across the transition to adulthood. • Attrition was high among young adults and replication trials are needed. [ABSTRACT FROM AUTHOR]