OBJECTIVES There is an attribution of smoking morbidity about 30% relate to lung cancer (LC), about 20% relate to cardiovascular diseases (CVD) eg. myocardial infarction (MI) and stroke and about 75% of patients with chronic obstructive pulmonary disease (COPD). The main objective of this study was to determine direct medical costs related to smoking in Slovakia and the defined costs of smoking cessation. METHODS Direct medical costs were evaluated from data collected in 2007 from the General Health Insurance Company, the largest one in Slovakia, covering 55% of all 5,400,000 inhabitants. The results were recalculated to the whole population. The costs were quoted in 2007 prices. RESULTS The smoking costs of those patients treated on LC were €19,726,950; on COPD they were €19,454,040; on stroke they were €6,019,778 and on MI they were €26,247,289. It was 33.66% from total direct costs €212,243,357 assigned to these diseases and 2.15 % of total Slovakia health care budget. The cost of treating a smoker on diseases associated with smoking was €1,114. Decreasing the number of smokers by 10% will reduce health care costs by €7,144,806 per year, i.e. 0.22% from total budget. The cost of treatment to stop smoking using varenicline was €919 per patient. CONCLUSIONS The direct costs associated with smoking comprise an important part of total health care budget in Slovakia. They signalize the need to establish effective strategies for smoking cessation. 44% clinical effectiveness of varenicline shows to be a cost-effective way in reducting smoking and decreasing health care expenditures.