OBJECTIVES: Clinical smoking cessation interventions have been found to be highly cost‐effective. This study analysed the cost effectiveness of smoking cessation treatment with drug therapy in a healthcare plan. METHODS: A self-administered survey was conducted online for 97,983 beneficiaries of a health plan in Brazil. For a sample of 2,188 individuals, using categorical questions, we asked the interviewees if they smoked, never smoked or stopped smoking. The survey also assessed the quantity and time of use of tobacco. A control group was established in the proportion of 3:1. The cost-effectiveness ratio was estimated by the average cost per user who quit smoking compared to those individuals who, despite treatment, continued to smoke. The annual cost was evaluated in three ways: total cost of the health plan, cost per user, and expenditures for smoking cessation drugs. Statistical analysis used OpenEpi version 3.01 software, by calculating the relative and absolute frequencies, means and standard deviation. For analytical statistics, Chi-square tests (Mantel-Haenszel and Fisher's Exact), when p <0.005. RESULTS: From the sample, 3.5% were smokers (mean age 52 years, 48% male and 52% female). The use of the health plan by smokers beneficiaries was significantly higher than that of non-smokers for outpatient procedures (p <0.001; OR 3.11) and not significant in hospital events (p = 0.250; OR 3.89). The annual expenditure per smoker was US$ 1,248.00 versus US$ 849.87 in non-smokers (p <0.001; OR 4.40). Simulations of the incorporation by health plan of varenicline 12 weeks, bupropion generic 8 weeks and nicotine replacement therapy 12 weeks were performed in different success rate scenarios. CONCLUSIONS: Interventions to promote smoking cessation should be considered a standard of good practice in healthcare plans, but, in our study only bupropion was cost effective and should be part of a healthcare program.