Introduction: A high risk strategy is one of more strategies in public health. Smoking remains the most important contributor to the burden of disease in developed countries. Methods: A population-based multi-factorial intervention study, Inter99 (1999-2006), Copenhagen, Denmark, using a high risk strategy. All 2408 daily smokers were repeatedly offered individual face-to-face lifestyle counselling. Smokers in the high-intensity group were offered participation in smoking cessation groups. We measured point abstinence at 1, 3 and 5-year follow-up and compared with a control group, using adjusted intention-to treat analyses. Results: Compared with the control group it was twice as likely to be self-reported abstinent at 5-year follow-up in the high-intensity intervention group (OR: 2.19; 95%CI: 1.7-2.8; p < 0.001). The effect of the intervention was significant, even when comparing validated abstinence in the intervention groups with self-reported abstinence in the control group (OR: 1.38; 95%CI: 1.1-1.8; p = 0.014). Male gender, vocational training, higher age at onset of smoking, high knowledge of harm of smoking and lower tobacco consumption predicted abstinence. Conclusion: A high risk strategy showed a significant effect on smoking in the long term. Proactive recruitment, face-to-face setting, repeated offer of assistance to quit and a multi-factorial approach may explain the success of the intervention.