OBJECTIVES To evaluate the cost-effectiveness of smoking cessation interventions (SCI) in seven Latin American countries. METHODS The health economic model structure was defined after analyzing regional decision maker's information needs and the availability and quality of the required epidemiological data in the participating countries: Argentina, Bolivia, Brazil, Chile, Colombia, Mexico and Peru. A common methodology to retrieve local relevant information was convened and a first order Monte Carlo, or probabilistic microsimulation of individual patients was built, incorporating the natural history, costs and quality of life impact of all the tobacco-related diseases: coronary and non-coronary heart diseases, cerebrovascular disease, COPD, pneumonia/influenza, lung cancer as well as 9 other neoplasms. The public health perspective and standard discount rate were used. Interventions ranged from brief behavioural counselling to intensive pharmacological and cognitive behavioural therapy. RESULTS An initial validation against the Argentinean population showed adequate internal validity, with all simulated events rates falling within ±10% of the source publications. R2 between predicted and observed values ranged from 0.758 to 0.999. Third order validation showed an excellent correlation between published data and model results. Incremental Cost per QALY were calculated for different sets of interventions and target populations in each of the participant countries. Results in the cost effectiveness plane and acceptability curves were plotted. Cost per QALY showed great variability among treatments and countries. CONCLUSIONS The results of the HEM will allow decision makers in the participating countries to tailor coverage policies for tobacco cessation interventions based on the cost-effectiveness evaluated for each setting.