OBJECTIVES: Existing health economic evaluation models (HEEM) for smoking cessation interventions (SCI) share a common set of shortcomings related to state transition modeling approach, mainly memorylessness and mutually exclusive states. This project constitutes a collaboration among seven countries in Latin America (LA) in order to elaborate a common HEEM overcoming the aforementioned limitations. Our objective was to develop a common HEEM for SCIs applicable to different countries in LA. METHODS: After performing a systematic review of existing HEEM, two rounds of consultations with the seven participant countries and one team meeting in Buenos Aires, the final HEEM structure was convened. It was programmed in Microsoft Excel® using Visual Basic based Macro functions in order to simulate individual subjects' histories over their lifetime. Absolute risk of key events for the non-smoking subpopulation where derived from the population risks and corresponding relative risks. Model validation was done by comparing predicted death rates to Argentina's vital statistics. RESULTS: The HEEM developed calculates probabilistically the rate of occurrence of five conditions as well as their cost and mortality/quality of life impact: ischemic and non-ischemic heart disease, lung cancer, cerebrovascular and chronic obstructive pulmonary disease. These events are non-mutually exclusive., Validation was performed with 20 cohorts simulations of 50000 subjects in each age category (40, 50, 60 and 70 years) showing an excellent external validity (+/-5% of predicted values). CONCLUSION: This is the first multi-country collaborative project to our knowledge that validated and used a microsimulation model in order to evaluate the cost-effectiveness of SCI in LA.