en Aims: Drug abuse among college students continues as a major public-health concern. Theory-driven research is necessary to address and find causes. The current research investigates the utility of Theory of Planned Behavior (TPB) in designing and implementing a drug abuse educational prevention program among medical college students. Methods: This quasi-experimental study was conducted among 120 college students in two groups: experimental and control, who were randomly enrolled at the baseline survey. We used a questionnaire, which included three sections of background data (11 questions), knowledge about the side effects of drug abuse questionnaire (16 questions), and TPB-based questionnaire (20 questions). Educational planning was based on active learning with using group discussion, printed leaflet, and audio-visual CD. The participants were followed up after 2-month intervention. Data were analyzed by the SPSS software version 16 using appropriate statistical tests such as stepwise multiple logistic regressions and t-test. Findings: Almost 6.7% of the participants had a history of drug abuse. The three predictors of 1) attitude, 2) subjective norms, and 3) perceived behavioral control accounted for 48 % of the variation in the outcome measure of the intention to drug abuse. There was a significant improvement in average response for knowledge about the side effects of drug abuse and TPB variables among the students who were under intervention (P < 0.05). Conclusions: Designing intervention to reduce positive attitude and subjective norms toward drug abuse among college students could be useful to substance abuse prevention. Drug Abuse, Prevention, Health 41 52 http://hehp.modares.ac.ir/browse.php?a_code=A-5-1000-8230&slc_lang=en&sid=4