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Introduction: The elderly are among the main targets of influenza vaccination campaigns. Previous studies have shown that socio-economic status influences compliance with influenza vaccination, particularly in the elderly. Deprivation indexes can therefore be useful in identifying population groups with lower vaccination uptake and guide targeted intervention to improve vaccination coverage. We analysed the correlation between influenza vaccination coverage and levels of socio-economic and health deprivation among the population of Cagliari, by means of an Index of Socio-Economic and Health Deprivation (SEHDI) specifically tailored to the city, in order to identify population subgroups needing specific intervention to improve vaccination coverage., Methods: A combination of linear regression, factor analysis and cluster analysis was adopted in order to build the SEHDI at the Census Tract (CT) level; data were taken from the 2011 Italian Census. Mortality among subjects aged ≥ 65 years in Cagliari in the period 2013-2015 was used to select the SEHDI variables. On the basis of the SEHDI, his population was classified into five normalised deprivation groups. Information on vaccination coverage was provided by general practitioners and Local Health Units. Cause-specific mortality and information on vaccination coverage in the deprivation groups were analysed by means of ANOVA (F test at p < 0.05)., Results: Around 20% of the Cagliari population was seen to be living in disadvantaged conditions. The trends in Standard Mortality Rates (SMRs) for all causes and for respiratory diseases, chronic obstructive pulmonary diseases (COPD), influenza and pneumonia were analysed across the deprivation groups. Pneumonia and flu mortality rates displayed a non-linear trend in men and a positive linear trend in women. Flu vaccination uptake rates were low: 27%. Coverage proved to be lower in the two extreme categories and higher in the medium deprivation ones., Conclusions: The correlation between low vaccination coverage and socio-economic deprivation not only underlines the important role of vaccination in safeguarding health, but also the fact that it can be considered a factor in ensuring the system's equality, thanks to its role in limiting health impacts on those living in the most problematic or disadvantaged circumstances. It also stresses the characteristics which contribute to low compliance. Therefore, this finding should be taken into account in the organization of vaccination campaigns and should prompt differentiated interventions in each local area.