Background: To assess the long-term effectiveness of a community-based intervention on cigarette, passive, and hookah smoking in adolescent boys and girls. Methods: 1159 adolescents who participated in the Tehran Lipid and Glucose Study (TLGS) between 2001 and 2004 were followed for 12 years (every-three-year follow-ups). Participants in the intervention area received lifestyle interventions in the settings of family, schools, and community. After excluding those with missing baseline parental data (n=66), complete parental data of 1093 adolescents was used for cluster analysis, and families were classified as low- and high-risk. Afterward, 296 individuals who did not complete intervention/follow-ups were excluded. The GEE analysis was performed on 797 adolescents (369 boys) to assess the intervention effect on tobacco-related habits; 605 and 192 resided in the control and intervention area, respectively.Results: Mean age of adolescents was 15.21±1.95 years at baseline. Adolescents living in high-risk families were more at risk of cigarette, passive, and hookah smoking. The intervention decreased the odds of cigarette and passive smoking by 38% and 57%, respectively. The intervention was not successful in reducing the risk of hookah smoking in adolescents. After sex-specific analysis, the intervention reduced the risk of current cigarette smoking by 40% only in boys and passive smoking in both sexes.Conclusions: Targeting lifestyle behaviors in adolescents and their families in a community setting reduces cigarette smoking in school-aged boys and protects both sexes from secondhand smoke; findings that could be valuable for designing future health promotion interventions focusing on adolescents smoking.Trial registration: This study is registered at Iran Registry for Clinical Trials (IRCT), a WHO primary registry (http://irct.ir). The registry date is 29/10/2008; (IRCTID: IRCT138705301058N1).