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Influenza disease is a major cause of morbidity and mortality in the elderly and at-risk adults. Despite the international recommendations for vaccinating those at-risk populations, many countries still have not adopted this immunization program. The objective of the present study is to evaluate the long-term cost-effectiveness of influenza immunization in the elderly and at-risk adult populations, in the case of funding this vaccination program by health care payers. Because vaccination programs have long-term effects, modelling methods are particularly adapted to economic evaluations of immunization programs. Thus, by using the health care payers'' perspective, a Markov decision model has been designed for influenza vaccination program. Markov states and Markov cycle length have been defined according to disease epidemiology. The costs and effectiveness of vaccinating elderly and at-risk adults are compared with the costs and effectiveness of not vaccinating those populations. Epidemiological data that may be considered as international will be collected through publications, whereas countries'' specific data will be collected locally through a retrospective study. A case study will be presented for an Argentinean Managed Care Organization (MCO). Calculation method will be the Monte Carlo simulations'' one and cost-effectiveness ratios will be presented as cost per Life Year Gained and cost per case avoided. [Copyright &y& Elsevier]