OBJECTIVES: From a Danish perspective to analyse the incremental cost-effectiveness of the pharmacological smoking cessation therapy including counselling using varenicline (Champix®) compared with bupropion SR (Zyban®), nicotine replacement therapy (NRT) or smoking cessation courses (group based counseling). METHODS: A Markov model was developed using a hypothetical Danish cohort of smokers who made a single quit attempt (cycle length 1 year),. The direct costs of smoking cessation and treatment of smoking-related diseases (COPD, lung cancer, CHD, stroke and asthma exacerbations) were included (2006-prices). Future costs were discounted at 5%. The incremental cost-effectiveness was calculated as costs per quitter and costs per QALYs gained. The evidence for quit rates included head-to-head trials for varenicline versus bupropion, a Cochrane review of NRT (Stead et al., 2008) and a Danish cohort study of smoking cessation courses (Kjaer et al., 2007). The time horizons applied were 20-year and lifetime. RESULTS: Modelling results revealed that varenicline resulted in more quitters and fewer cases of smoking-related diseases. In a 20-year time horizon (lifetime) cumulative QALYs gained using varenicline were 1,04 (4237) compared with smoking cessation courses, and up to 2517 (5600) QALYs compared with NRT. The costs per additional quitter using varenicline instead of bupropion were DKK3060 (20-year), whereas varenicline was cost-saving compared with NRT and smoking cessation courses. With a lifetime perspective varenicline was always a cost-saving option in terms of cost per quitter. Resulting in more QALYs and fewer costs varenicline dominated the other alternatives, when lifetime was considered. With a 20-year time horizon, the costs per QALY gained for varenicline versus bupropion were DKK30,272, but varenicline still dominated NRT and smoking cessation courses.CONCLUSIONS: This cost-effectiveness analysis confirms that varenicline is a cost-effective strategy for smoking cessation in Denmark. This finding is in accordance with results found in Sweden and the Netherlands.