OBJECTIVES: To compare the budget impact in the main Public Health Institution in Mexico due to the use of MF59-adjuvanted vaccine (MF59), split vaccine (SPL) and a No Vaccination Program Alternative (NOVA) in Mexican elderly population. METHODS: A budget impact analysis considering a public health institution perspective was performed. The expenses of the Mexican Health Care System due to a vaccination program (vaccines, vaccination program, medical visits, treatment of influenza and influenza related complications, hospitalization and intensive care unit cost) were simulated with MF59 or SPL versus NOVA in elderly population affected by an influenza pandemic. A case scenario of high incidence influenza (5% of population) with three sub-scenarios was designed: a) 20%, b) 30%, and c) 50% of patients developing complications related to influenza.  A systematic literature review was designed in order to include the most recent information about vaccines effectiveness measured as the ability of provide seroprotection against Influenza A/H1N1 strain and pandemic historical influenza incidences recommended by World Health Organization. Use of resources and cost matrixes were designed with the most recent data of main Public Health Institution in Mexico, which attends about fifty percent of the total population in Mexico.   RESULTS: The cost of treatment of influenza and complications related to influenza were estimated in US$38.84 and US$5,052.06, respectively. Simulating prevention of influenza pandemic affecting 5% of Mexican elderly population results in less expenses for Public Health Institutions when MF59 is used in vaccination program compared to SPL and NOVA without varying the proportion of patients getting complications related to influenza (20%: MF59-US$69,833,474.83; SPL-US$84,692,366.64; NOVA-US$236,082,644.63. 30%: MF59-US$84,610,768.22; SPL-US$117,657,098.05; NOVA-US$349,754,132.23. 50%: MF59-US$113,903,164.91; SPL-US$183,586,560.86; NOVA-US$577,097,107.44). CONCLUSIONS: Using an MF59-adjuvanted vaccine as a preventive alternative in an Influenza Pandemic affecting elderly population in Mexico, represents important savings for Mexican Public Health Institutions compared to SPL and NOVA.