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Acute hematogenous osteomyelitis, septic arthritis, and their combination are considered to warrant especially aggressive treatment if caused by Staphylococcus aureus.Our prospective treatment trial of children aged 3 months to 15 years included 199 cases of S. aureus osteomyelitis, septic arthritis, or their combination. These cases were compared with 66 cases caused by other agents, mainly Haemophilus influenzae type b, Streptococcus pneumoniae, or Streptococcus pyogenes. According to protocol, the treatment was initiated intravenously only for 2 to 4 days and completed orally. Nonstaphylococcal and staphylococcal infections were treated similarly. Primary antibiotics were clindamycin or a first-generation cephalosporin. Follow-up lasted ≥12 months posthospitalization.Staphylococcal infections did not significantly differ in the duration of medication, hospital stay, surgery performed, or the number of sequelae when compared with the other etiologic groups. One child with S. aureus arthritis developed 2 late infections by other agents in the same anatomic site. Except 3 mild sequelae (2 caused by S. aureus and 1 by S. pyogenes) 12 months posthospitalization, all patients recovered completely.Osteoarticular infections of childhood caused by methicillin-susceptible S. aureus can be treated according to the same protocol as those used for infections caused by other agents.