BACKGROUND: The etiological profile of viruses among adult patients with community-acquired pneumonia (CAP) has not been characterized yet. The aim of this study was twofold: first, investigate the pathogen profiles and the molecular epidemiology of respiratory viruses among Japanese CAP patients; and second, explore the clinical significance of viral infections. METHODS: A cross-sectional observational study was conducted at Kyorin University Hospital. To identify respiratory pathogens, hospitalized CAP patients were enrolled, and reverse transcriptase-polymerase chain reaction technology was applied alongside conventional microbiological methods. Phylogenetic and pairwise distance analyses of 10 viruses were performed. CAP patients were divided into four etiological groups (virus alone, bacteria alone, co-detection of virus and bacteria, and not detected) and the clinical findings were compared. RESULTS: Seventy-six patients were enrolled. Bacteria alone were detected in 39.5% (n=30) of CAP patients. Virus alone or co-detection were found in 10.5% (n=8) and 11.8% (n=9) of cases, respectively. Streptococcus pneumoniae and human metapneumovirus were the most frequently detected bacterium and virus, respectively. Phylogenetic analyses of human metapneumovirus, human rhinovirus, and human respiratory syncytial virus showed that different subgroups and genotypes might be associated with CAP. Respiratory failure was more common when a virus was detected (both virus alone and co-detection groups; n=17, 100%, p<0.05) than when a bacteria alone was detected (n=17, 56.7%). CONCLUSION: Prevalence of respiratory virus infection in CAP inpatients was 22.3%. The detected viruses display high genetic divergence and correlate with increased respiratory failure.