ABSTRACT Objective This study aimed to develop and assess a tailored community-based intervention protocol for preventing substance use based on social cognitive theory in adolescents. Methods A tailored community-based substance use prevention intervention was undertaken with 140 boys and girls (14-18- years old) participating in the study in Isfahan, Iran. The intervention group attended eight 45-minute theory-based sessions based on social cognitive theory from 2018 to 2020. Data were analyzed 6, 18, and 24 months later by the SPSS.23 software. Results Social cognitive theory indicators, including positive outcome expectancies (p < .001, F = 25, ES = 0.34), negative outcomes expectancies (p < .001, F = 31.2, ES = 0.38), and self-efficacy (p < .001, F = 12.3, ES = 0.45) showed significant improvements at three stages (6, 18, and 24 months after intervention). The program also demonstrated significant but low effect size reductions in the incidence of cigarette (ES = 0.15), alcohol (ES = 0.05), and other drug use (ES = 0.01) in the intervention group among three follow-ups. Conclusion The results support the effectiveness of the community-based intervention program based on social cognitive theory in reducing the incidence of substance use among Iranian adolescents.