OBJECTIVES: To estimate costs and benefits of a preventive anti-influenza vaccination in a group of employees of ULSS 17 (an public health care district), in order to define a scheme of cost-benefit analysis to be used for other strategies of vaccination and in other contexts. METHODS: In an observational study conducted from December 2002 to April 2003, 107 employees (about 5% of the whole staff of ULSS 17), who voluntarily underwent the vaccination, were compared with 107 non-vaccinated employees working in the same context and matched for age, gender and working category. The outcome was evaluated by checking records from the personnel department about absence from work and related causes, including influenza. Costs and benefits of the anti-influenza vaccination from the ULSS point of view were subsequently calculated. RESULTS: Among vaccinated people absences from work were 23% less than among non-vaccinated and working days lost were 30% less than non vaccinated employees. The ratio between the benefits of the vaccination strategy (less working days lost) and its cost was 4.2. The convenience emerges also through the sensitivity analysis, which took in consideration the mean cost of a working day for the enrolled employees, it showed that the cost-benefit ratio range from 4.5 to 11.7. CONCLUSIONS: The results of this study suggest that the implementation of the anti-influenza vaccination strategy in ours sample of working people was cost saving. The cost-benefit analysis used in this study could also be used for other vaccination strategy and in other contexts.