OBJECTIVES: influenza vaccination has proven effective in the reduction of influenza-like illness ( ILI) cases and influenza-related hospitalisations, drug consumption, primary care consultations and deaths in the elderly population. The aim of this study is to assess the economic impact in Italy of different prophylactic strategies (vaccination with a standard vaccine and with the innovative MF59® adjuvated vaccine versus no intervention). METHODS:  A pharmacoeconomic simulation model has been developed. Health economics and demographic data are taken from specific Italian sources and vaccine effectiveness data derived from published. Direct sanitary costs are considered according to current Italian prices and tariffs. RESULTS: A total of 9,800,000 of the about 12,000,000 people of 65+ years residence in Italy can be considered at high risk for influenza complications due to underlying chronic diseases. Absence of vaccination could lead to more than 2 million ILI cases, and 30,000 related deaths. The vaccination programme would lead to an estimated 1.5 million ILI cases with a standard vaccine and to 1.3 million with the MF59® adjuvated vaccine. The standard vaccination strategy could produce a moderate direct cost increase of about €45 million (+4.3%), whereas the adjuvated vaccine could provide an estimated saving of about €80 million (-7.9%), both compared to the null option. Cost savings are mainly related to hospital admissions avoided. The incremental cost-effectiveness ratio (ICER) of the standard vaccine vs. no vaccination strategy is of €85.68/ILI avoided, and of €4,411.42/death avoided. The strategy based on the MF59® adjuvated vaccine dominates the other two options. CONCLUSIONS: Vaccination with the MF59® adjuvated vaccine is more effective and cost saving when compared with the standard vaccination or no vaccination, thus representing the optimal strategy for the elderly population. The standard vaccine, even though a light cost increase, proved to be cost effective compared to the null option.