This randomized controlled trial evaluated the effectiveness of a multicomponent Health Promoting Schools (HPS) intervention program in improving self-reported smoking outcomes among a cohort of adolescents in 22 public secondary schools in the Hunter Region of New South Wales, Australia. Pre-test surveys were completed by students in the first 2 years of secondary school, with a 2-year post-test survey. Multivariate analyses examined intervention effect for the main outcome, post-test smoking behavior, controlling for pre-test smoking status, school and other confounders. The sample comprised the cohort of 1852 students who completed both surveys. The results demonstrated that the HPS program failed to improve smoking behavior over the 2 years (equal increase of 10% in both groups). The program was successful in improving smoking knowledge, but not attitudes, in intervention versus control group (P < 0.001). Independent predictors of post-test smoking included: pre-test smoking [odds ratio (OR) = 5.44; 95% confidence interval (CI) = 3.20-9.28], being female (OR = 0.55; CI = 0.35-0.87), having more close friends who smoked (OR = 1.42; CI = 1.33-1.52), peer group having no clear opinion about smoking (OR = 3.23; CI = 1.27-8.27), having more positive and less negative attitudes towards smoking, and being less involved in school activities. We discuss methodological issues in multicomponent community-based interventions, and highlight the strengths and limitations of this study.