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Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection in children less than 5 years of age. The impact of non-RSV respiratory virus coinfection on the severity of RSV disease is unknown.This hospital-based prospective study was conducted in Nagasaki, Japan, on all children less than 5 years of age with acute respiratory infection (ARI) who had undergone a rapid RSV diagnostic test between April 2009 and March 2010. Thirteen respiratory viruses were identified from nasopharyngeal swab samples using a multiplex polymerase chain reaction; polymerase chain reaction–positive samples were considered as confirmed respiratory virus infections. The cases were classified into 3 categories (pneumonia, moderate-to-severe nonpneumonic ARI and mild ARI) according to the findings of the chest radiograph and the hospitalization records.Among 384 cases enrolled, 371 were eligible for analysis, of whom 85 (23%) were classified as pneumonia cases; 137 (37%) as moderate-to-severe nonpneumonic ARI cases and 162 (40%) as mild ARI cases. RSV was detected in 172 cases (61.6%), and 31 cases (18.0%) had double or triple infections with other respiratory viruses. RSV infection was more frequently observed in pneumonia cases (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.31–3.9) and moderate-to-severe nonpneumonic ARI cases (OR: 2.95; 95% CI: 1.82–4.78) than in mild ARI cases. The association with moderate-to-severe nonpneumonic ARI cases was stronger with RSV/non-RSV respiratory virus coinfection (adjusted OR: 4.91; 95% CI: 1.9–12.7) than with RSV single infection (adjusted OR: 2.77; 95% CI: 1.64–4.7).Non-RSV respiratory virus coinfection is not uncommon in RSV-infected children and may increase the severity of RSV disease.