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This study evaluated the effectiveness of a drug and violence resistance educational program (Programa Educacional de Resistência às Drogas e à Violência-PROERD) on latent substance use profiles over a 9-month follow-up period. Two PROERD curricula were evaluated through a cluster randomized controlled trials with two parts that included a total of 4030 fifth-and seventh-grade students in 30 public schools in São Paulo. The intervention groups received 10 PROERD classes delivered by trained police officers, while the control group received no intervention. The primary outcome measures were drug use (any alcohol use, binge drinking, tobacco, marijuana, and inhalants) in the past 6 months, which was assessed using a pretest and a posttest 9 months later. Latent transition analysis was employed to investigate the effect of the intervention on the probabilities associated with the transition across drug use profiles. Latent drug use profiles are underlying subgroups of individuals similar to each other regarding their pattern of polysubstance use. Two different latent drug use profiles were revealed among the fifth graders (abstainers/low users and alcohol users/binge drinkers) and three drug use profiles among the seventh graders (abstainers/low users, alcohol users/binge drinkers, and polydrug users). For both, there was no evidence of the effect of PROERD on drug transition probabilities. In conclusion, the intervention was not successful in changing transitions across adolescent drug use profiles. Thus, the failure of the intervention to affect students' substance use profiles suggests that it should be reconsidered before it is implemented further in Brazilian schools., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)