BACKGROUND: The relative impact of human rhino/enteroviruses (HRV/EV) compared to influenza viruses on hospitalized children is unknown. OBJECTIVES: This retrospective study compared the epidemiology and clinical characteristics of hospitalized patients with HRV/EV to patients hospitalized with influenza virus. STUDY DESIGN: Respiratory specimens from hospitalized children submitted between January 1, 2009 and December 31, 2009 to Children\'s Hospital Colorado Virology Laboratory in Aurora, CO were tested by a commercial multiplex PCR for 16 respiratory viruses and subtypes. Patients with specimens positive for HRV/EV or influenza virus without bacterial or viral co-infection were selected for retrospective chart review. RESULTS: Of the 2299 patients with specimens tested during the study period, 427 (18.6%) were singly positive for HRV/EV and 202 (8.8%) for influenza virus (p<0.01). Children with HRV/EV were more likely to present with increased work of breathing (67.9% vs. 52.5%, p<0.01) with crackles (36.3% vs. 23.3%, p<0.01) and wheezing (41.7% vs. 22.8%, p<0.01) noted on exam. Children hospitalized with HRV/EV had a shorter median length of stay (2 days vs. 3 days, p<0.01), duration of fever (1 days vs. 3 days, p<0.01), and duration of hypoxemia (2 days vs. 3 days, p<0.01) than children with influenza virus. Similar percentages of children with HRV/EV and influenza virus were admitted to the PICU and required positive pressure ventilation. There were no deaths in children hospitalized with HRV/EV, whereas 6 children with influenza virus expired. CONCLUSIONS: HRV/EVs are common pathogens in hospitalized children associated with serious lower respiratory tract disease and significant morbidity, similar to influenza viruses.