OBJECTIVES: To assess the cost-effectiveness of bupropion and nortriptyline compared with placebo using governmental perspective in Thailand. METHODS: A decision tree and Markov model were used to simulate the effects of cessation on cohorts of 10,000 male smokers with age of 40 who smoke regularly 10-20 cigarettes per day. An incremental cost-effectiveness ratio of bupropion and notriptyline compared to placebo was estimated using health care system persepctive.Transition probabilities were obtained from literature reviews, while medical care costs and utilization patterns were derived from database of a Thai tertiary care hospital and literatures. The efficacy of bupropion and nortriptyline was obtained from a Bayesian meta-analysis. Costs of the medications were obtained from the Thai Drug and Medical Supply Information Center. Both costs and outcome were discounted at three percent. All costs were presented in 2005 Thai Baht. A series of sensitivity analysis including probabilistic sensitivity analyses and cost-effectiveness acceptability curve were performed. RESULTS: In comparison to placebo, bupropion results in cost-savings of BAHT11,403.07 (US$346) to the health system and life year gains of 0.140 years, while nortriptyline leads to costs-savings of BAHT12,223.18 (US$370) and life year gains of 0.109 years. Probabilistic sensitivity analyses and cost-effectiveness acceptability curves demonstrate that the probability of using bupropion and nortriptyline for smoking cessation being cost-saving are 80% and 99%, respectively. CONCLUSIONS: From the perspective of the health care system, both bupropion and nortriptyline yield cost-savings and life year gains. These findings should raise a flag for Thai policy-makers to consider the use of bupropion and nortriptyline for Thai smokers as potential cost-saving medications.