The aim of this multicentre study was to assess incidence of influenza like illness (ILI) among Italian medical residents (MRs) during 2011-2012 influenza season, to detect variables associated with ILI and to compare estimated ILI incidence among MRs and general population. A cross-sectional survey was carried out throughout an anonymous questionnaire administered to all MRs attending the post-graduate medical schools of 18 Italian Universities. At the same time an analysis of the ILI incidence in the Italian general population was conducted through the Italian Influenza Surveillance Network. Of a total of 2,506 MRs, 1,191 (47.5%) reported at least one ILI episode. A higher proportion of ILIs was reported by MRs of Central (25.0% with ILI vs 20.2% without ILI) and Southern Italy (40.2% with ILI vs. 36.4 without ILI) compared to Northern Italy (34.8% with ILI vs. 43.4% without ILI) (p<0.001). Italian MRs had a higher cumulative incidence of ILIs (546.7 episodes per 1,000 vs. 75.9 episodes per 1,000) and an earlier peak (January 2012 vs. February 2012), compared to general population due to higher number of contacts in hospital setting. MRs reported a high rate of ILI infection probably in association with their working activities. These data suggest the need to offer an earlier influenza vaccination to HCWs than general population with the aim to both prevent ILI and its transmission to patients.