BACKGROUND. Staphylococcus aureus strains carrying the genes encoding Panton-Valentine leukocidin (pvl-positive [pvl(+)]) are associated with more febrile days and higher complication rates of osteomyelitis in children than are pvl-negative (pvl(-)) strains. OBJECTIVES. Selected clinical, laboratory, and radiographic findings in children with osteomyelitis caused by pvl(+) and pvl(-) S aureus strains were compared. METHODS. The demographics, selected clinical features, laboratory values, and radiographic findings of children with community-acquired S aureus osteomyelitis prospectively identified at Texas Children's Hospital between August 2001 and July 2004 were reviewed. Polymerase chain reaction was performed to detect the genes for pvl (luk-S-PV and luk-F-PV) and fibronectin-binding protein ( fnbB) in S aureus isolates. chi(2), 2-sample t test, and multiple logistic regression were used for statistical analysis. RESULTS. Methicillin-susceptible and methicillin-resistant S aureus (MSSA and MRSA, respectively) caused osteomyelitis in 33 and 56 children, respectively. Twenty-six isolates were pvl(-) (26 MSSA), 59 were pvl(+) (3 MSSA, 56 MRSA), and 4 were not available for analysis (4 MSSA). On univariate analysis, patients with pvl(+) S aureus isolates had significantly higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level both at presentation and as a maximum value during hospitalization and were more likely to have a blood culture positive for S aureus during their admission. Patients with pvl(+) S aureus isolates were significantly more likely to have concomitant myositis or pyomyositis compared with patients with pvl(-) S aureus isolates on MRI. In a multivariate analysis pvl remained significantly associated with ESR and CRP levels at presentation and blood culture positive for S aureus. pvl(+) status and younger age were associated with myositis on MRI. CONCLUSIONS. Osteomyelitis caused by pvl(+) S aureus strains were associated with more severe local disease and a greater systemic inflammatory response compared with osteomyelitis caused by pvl(+) S aureus.