OBJECTIVES: Varenicline (Champix®) is a new drug indicated for smoking cessation. The objective was to analyse the efficiency of varenicline compared with bupropion, NRT (nicotine replacement therapy) and no pharmacological treatment in Spain. METHODS: A Markov model was developed to analyse the health and economic consequences of smoking cessation therapies. The transition probabilities of morbidity and mortality and the efficacy were taken from published studies. The model allows cost effectiveness analyses for different time frames (10 years, 20 years and life time). Outcomes are measured in terms of incremental life years gained (LYG) and QALYs. Pharmacological costs and costs of medical visits for the treatment with varenicline and bupropion were considered. Treatment costs of smoking associated morbidity were taken from Spanish studies. Results were expressed in terms of incremental cost per life year gained and incremental cost per QALY of varenicline versus comparators. The analyses were done under the perspective of the National Health System, discounting costs and health benefits at 3 percent. RESULTS: The life time cost-effectiveness analysis shows that varenicline dominates all other smoking cessation interventions (more effective at a lower cost). This is due to the higher efficacy of varenicline associated with a reduction in smoking related morbimortality, which, in the long term, accounts for health care cost savings that overcome the extra cost of varenicline. When shorter timeframes are considered, varenicline presents values under 9.000 €/QALY and 50.000 €/QALY (analyses at 20 and 10 years respectively). CONCLUSION: Varenicline is a dominant option (more effective at a lower cost) compared with all other smoking cessation treatments when the timeframe is the life span of the patient. Varenicline is cost-effective even when shorter timeframes are considered (20 years or more), with an estimated incremental cost per QALY well bellow the threshold commonly accepted in our environment: 30,000€/QALY.