Since research shows that interactive prevention programs are more effective than didactic-based lectures, the current study examined the efficacy of an interactive substance abuse prevention program for adolescents. Participants completed pre- and post-surveys examining their substance use knowledge and program perceptions. The program included small groups led by near-peer health care professional trainees as facilitators and interactive, hands-on activities, such as the examination of diseased human organs due to substance use. Results demonstrated statistically significant increases in knowledge of substance use risks on mental and physical health. Findings highlight effective methods that can be implemented by health care professionals to increase awareness of the harmful effects of substance use.