The present study examined parenting style dimensions (demandingness and responsiveness) as predictors of adolescent drug use and also evaluated whether parenting styles dimensions moderate the effects of the implemented prevention program. 6.391 students in the 7th and 8th grades at 72 Brazilian public schools participated in a three-wave randomized controlled trial to evaluate a school drug-use prevention program. We used structural equation modeling to test if baseline parenting style dimensions (demandingness and responsiveness) would predict the use of drugs (alcohol, binge drinking, cannabis, inhalants, and tobacco) after 21 months. Additionally, we evaluated an interaction version of the above-described model to test if the effect of the prevention program would be moderated by either or both parenting style dimensions. Higher levels of parent demandingness predicted lower chances of adolescent drug use (e.g., Cigarette use OR 0.76, 95% CI 0.64–0.89); responsiveness on the five outcomes showed p value superior to 0.01. The effect of the #Tamojunto intervention is unlikely to be conditioned to either parenting style dimensions on the assessed outcomes. Clinical trial registration Brazilian Register of Clinical Trials (REBEC): #RBR-4mnv5g (https://www.ensaiosclinicos.gov.br/rg/?q=tamojunto).