The aim of this longitudinal study was to determine the effect of an original prevention program (RAPP) on the behavioral and cognitive characteristics of adolescents with high risk for substance consumption. Seventy-six Mexican adolescents 12–15 years old (38 with high risk (HR) and 38 with low risk (LR)) were selected. RAPP was applied for 3 months. Resilience, social skills, attitudes towards substance use, ability to delay a reward, and inhibitory control were assessed in these adolescents, before and after the RAPP intervention. Both groups improved their scores; however, HR achieved greater changes than LR. Findings suggest that HR have behavioral characteristics that can be considered as risk factors for substance consumption (low levels of resilience, low social skills, little family support, positive attitudes towards substance use). RAPP proved to be an effective program for preventing these risk factors for substance use in adolescents.