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Background: Smoking prevention programs have been taught in schools to reduce the high smoking prevalence and its related problems among adolescent populations. Although short-term benefits have been observed, the long-term effectiveness of such programs appear to be inconsistent. This study aims at investigating the long-term impact of both health and Islamic focused interventions amongst students in Indonesia.Methods: At 6 months after completion of the interventions, 427 of the original 447 participants (control group = 128, intervention groups = 299) from a school-based cluster randomized control trial were re-assessed for their smoking knowledge, attitudes, intentions and behaviours using a self-report questionnaire. Data was analyzed according to the study's 2 × 2 factorial design with adjustment for baseline scores, school and classroom clustering effects and multiple comparisons.Results: Compared to the control group, significant long term effects were found for the health-based intervention program in improved health (β = 4.3 ± 0.4, p < 0.001), Islamic (β = 1.1 ± 0.4, p = 0.01) knowledge and a reduction of smoking attitudes (β = -11.5 ± 1.8, p < 0.001). For the Islamic-based intervention programs there was an improvement of health (β = 3.7 ± 0.4, p < 0.001) and Islamic (β = 2.2 ± 0.5, p < 0.001) knowledge and a reduction towards smoking attitude (β = -6.0 ± 1.9, p < 0.01) and smoking behaviors in the past month (OR = 0.1, 95 % CI = 0.0-0.8, p = 0.03). The effects were greater but less than additive in the combined group for health (β = -3.2 ± 0.9, p < 0.001 for interaction) and Islamic knowledge (β = -2.3 ± 0.9, p = 0.01 for interaction) but were additive for smoking attitudes (β = 6.1 ± 3.2, p = 0.07 for interaction). No significant effects on smoking intentions were observed at 6 months follow-up in the health or Islamic-based intervention programs.Conclusion: School-based programs can provide long term benefits on Indonesian adolescents' smoking knowledge and attitudes. Tailoring program intervention components with participants' religious background might maximise program effectiveness. A larger and more encompassing study is now required to confirm the effectiveness of this new Indonesia culturally-based program. Adolescents in similar areas might also benefit from this type of school-based smoking cessation program.Trial Registration: Australian New Zealand Clinical Trial Registry, ACTRN12612001070820. [ABSTRACT FROM AUTHOR]