This study examined the characteristics of culture-negative osteoarticular infections (OAIs) during the emergence of methicillin-resistant Staphylococcus aureus. Culture-negative OAIs were mild compared with culture-positive infections, especially those caused by methicillin-resistant Staphylococcus aureus. Despite no increase in severity during the study period, the duration of parenteral antibiotics for children with culture-negative OAIs more than tripled in 2004-2008 compared with 2002-2003.