Introduction: Influenza viruses are the major respiratory pathogens worldwide and high-risk groups such as healthcare workers may develop severe forms of the disease. The purpose of this study was to evaluate the cost-effectiveness of influenza vaccination for 4 target groups including pregnant women, elderly people (aged over 65 years), healthcare workers and school-age children in Iran. Methods:A cost-effectiveness analysis using a decision tree model over a one-year time horizon for the influenza vaccination versus no vaccination in Iran was carried out according to the prospective of the Ministry of Health. Epidemiological data were extracted from the relevant local databases and the literature. The medical and community care costs with sampling of the patients in all 4 groups were estimated.Results:The results of the economic evaluation showed that in Iran, incremental costs per Disability-Adjusted-Life-Years (DALY) of influenza were estimated to be US$ 15,069, US$ 104,104, US$ 5,685 and US$ 14,983 for the pregnant women, the elderly people, the healthcare workers and the school-age children, respectively.Conclusion: The results of this study indicated that the implementation of influenza vaccination program might be cost effective only for the healthcare workers.