Respiratory tract infections account for high morbidity and mortality around the world. Fragile patients are at high risk of developing complications such as pneumonia and may die from it. Limited information is available on the extent of the circulation of respiratory viruses in the hospital setting. Most knowledge relates to influenza viruses (FLU) but several other viruses produce flu-like illness. The study was conducted at the University Hospital Policlinico Tor Vergata, Rome, Italy. Clinical and laboratory data from hospitalized patients with respiratory tract infections during the period October 2016-March 2019 were analysed. The retrospective analysis included 17 viral agents detected by FilmArray test and clinical data from medical records and hospital discharge sheets. Models were adjusted for relevant confounders such as clinical severity and risk of death, socio-demographic characteristics and surgical procedures. From a total of 539 specimens analysed, 180 (33.39%) were positive for one or more respiratory viruses. Among them, 83 (46.1 %) were positive for influenza viruses (FLU), 36 (20%) rhino/enteroviruses (RHV/EV), 17 (9.44%) human coronaviruses (HCOV-229E, -HKU1, -NL63, and -OC43), 17 (9.44%) respiratory syncytial virus, 15 (8.33%) human metapneumovirus (HMPV), 8 (4.44%) parainfluenza viruses (PIV) and 4 (2.22%) adenoviruses (ADV). The distribution of viral agents varied across age groups and month of detection. The positive specimens were from 168 patients [102 M, 66 F; median age (range): 64 years (19−93)]. Overall, 40% of them had a high-grade clinical severity and a 27% risk of death; 27 patients died and 22 of them (81.5%) had received a clinical diagnosis of pneumonia. Respiratory viral infections may have a severe course and a poor prognosis in hospitalized patients, due to underlying comorbidities. Monitoring the circulation of respiratory viruses in hospital settings is important to improve diagnosis, prevention and treatment.