Kawasaki disease (KD) is a disease of unknown cause. To investigate the infectious etiology of Kawasaki disease, we initiated a prospective case-control study to investigate possible links between common viral infections and Kawasaki disease. Methods: We enrolled 226 children with KD and 226 age- and sex-matched healthy children from February 2004 to March 2010. Throat and nasopharyngeal swabs were taken for both viral isolation and polymerase chain reaction (PCR) for various viruses. Results: The mean age of the 226 KD cases was 2.07 years, and the male to female ratio was 1.43 (133 boys to 93 girls). Their mean fever duration was 7.5 days with a mean peak temperature of 39.7°C. In addition to the typical symptoms of fever, neck lymphadenopathy, lip fissure and/or strawberry tongue, skin rash, nonpurulent bulbar conjunctivitis, palm/sole erythema, and induration followed by periungual desquamation, these KD cases also exhibited cough (69%), rhinorrhea (58%), and diarrhea (45%). Cases of KD had a significantly higher positive rate of viral isolation in comparison with the control group (7.5% vs. 2.2%, p = 0.02). Compared with the control group, cases of KD were more likely to have overall positive rates of viral PCR (50.4% vs. 16.4%, p < 0.001) and for various viruses including enterovirus (16.8% vs. 4.4%, p < 0.001), adenovirus (8.0% vs. 1.8%, p = 0.007), human rhinovirus (26.5% vs. 9.7%, p < 0.001), and coronavirus (7.1% vs. 0.9%, p = 0.003). Conclusion: We found that some common respiratory viruses, such as adenoviruses, enteroviruses, rhinoviruses, and coronaviruses, were associated with KD cases.