Background: Acute respiratory tract infections are commonly caused by viruses in children. The differences in clinical data and outcome between single and multiple viral infections in hospitalized children were analyzed. Methods: We retrospectively reviewed the medical records of hospitalized children who had fever and a xTAG Respiratory Virus Panel (RVP) test over a 2-year period. The clinical data were analyzed and compared between single and multiple viral infections. Viral etiologies in upper and lower respiratory infections were analyzed and compared. Results: A total of 442 patients were enrolled. Patients with positive viral detection (N Z 311) had a significantly lower rate of leukocytosis (p Z 0.03), less evidence of bacterial infection (p Z 0.004), and shorter duration of hospitalization (p Z 0.019) than those with negative viral detection. The age of patients with multiple viral infections was younger than those with single viral infection; however, there were no significant differences in duration of fever, antibiotics treatment and hospitalization between these two groups.The most commonly identified virus was human rhinovirus. About 27% (n Z 83) of patients had multiple viral infections. Overall, the highest percentage of human bocavirus infection was detected in multiple viral infections (79%). Lower respiratory tract infection (LRTI) was Journal of Microbiology, Immunology and Infection (2019) 52, 902e910 independently associated with multiple viral infections (p Z 0.022), respiratory syncytial virus (RSV) infection (p Z 0.001) and longer hospitalization duration (p Z 0.011). Conclusion: Multiple viral infections were associated with younger age and a higher risk of developing LRTI. However, multiple viral infections did not predict a worse disease outcome. More studies are needed to unveil the interplay between the hosts and different viruses in multiple viral infections.