The role of influenza virus in patients presenting at ED during seasonal-epidemic periods has not previously been specified. Our objective was to determine its frequency according to clinical presentation. This is a prospective observational study conducted during three-consecutive seasonal Influenza epidemics (2013-2015), including patients presenting i) community-acquired pneumonia (CAP); ii) severe acute symptoms (SAS): respiratory failure (RF), hemodynamic failure (HF), cardiac failure (CF), and miscellaneous symptoms (M); iii) symptoms suggesting influenza (PSSI). Patients were tested for influenza using specific PCR on naso-pharyngeal swabs. Of 1,239 patients, virological samples were taken from 784 (63.3%), 213 (27.2%) of whom were positive for the influenza virus: CAP 52/177 (29.4%), SAS 115/447 (25.7%) and PSSI 46/160 (28.8%) (p = 0.6). In the SAS group positivity rates were: RF 76/263 (28.9%), HF 5/29 (17.2%), CF 15/68 (22.1%), and M 19/87 (21.8%) (p = 0.3). Among the major diagnostic categories, the influenza virus positivity rates were: asthma 60/231 (26%), acute exacerbation of chronic obstructive pulmonary disease 18/86 (20.9%), HIV 5/21 (23.8%) and cardiac failure 33/131 (25.2%). The positivity of the samples has not been associated (p>0.1) nor the presence of signs of severity or admission rate in medical ward nor intensive care unit. Our results indicate that during seasonal influenza epidemics, Influenza virus-positivity rate is similar in patients attending ED for influenza-compatible clinical features, patients with acute symptoms including pneumonia, respiratory, hemodynamic and cardiac distress, and patients presenting for acute decompensation of chronic respiratory and cardiac diseases.