OBJECTIVES: Although most deaths from influenza occur among elderly people, all age groups are affected by influenza infections. This illness is responsible for significant epidemiological and economic burden to the working age population. Influenza vaccination has been demonstrated to reduce this impact, however few information concerns Eastern Europe countries. This study was designed to determine the effectiveness of influenza vaccination in healthy working adults in Russia and the economic benefits of such a program from an employer perspective. METHODS: A prospective, non-randomized, non-placebo cost-benefit study was conducted involving two groups: vaccinated and non-vaccinated. A 9-month follow-up was done (October 2005 - May 2006) using different questionnaires: one at inclusion to collect general employee information; an other one, one week after vaccine injection to collect post-vaccination adverse events; and the last questionnaire was used monthly to collect Influenza Like Illness (ILI) events, duration of symptoms and sick leave associated. Effectiveness calculations and cost-benefit analyses were performed to evaluate the impact of influenza vaccination program in optimizing the productivity of employee and the return on investment for the employer. RESULTS: In all, 1331 volunteers joined the study: 630 in the vaccinated group and 701 in the non-vaccinated group. The attack rate of ILI was lower among vaccinated (6.8%) than non-vaccinated subjects (23.2%). The effectiveness rates of influenza vaccine have reached 70.4% in reducing ILI occurrence and 80.8% in reducing sick leave days. 5.4€ per employee were invested for the vaccination. Assuming that employees working while experiencing ILI symptoms have a reduced level of productivity (30 to 70% of normal), the mean cost of disease avoided thanks to vaccination was between 7.5 and 10.8€. CONCLUSION: This study showed that ILI episodes had significant impact on work productivity. Influenza vaccination programs can decrease this impact and leads to cost-saving for the employer.