OBJECTIVES To assess clinical characteristics and differences in outcomes between children with Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) osteomyelitis or septic arthritis and whether initial antibiotic regimen affects patient outcomes.STUDY DESIGN We analyzed records of children ages 15 days to 18 years admitted between 2009 and 2016 to two tertiary children’s hospitals who were diagnosed with an osteoarticular infection and had a microorganism identified. We compared the relationship of MRSA versus MSSA and initial antibiotic selection on patient outcomes including length of hospitalization and requiring a PICU transfer.RESULTS A total of 584 patients met inclusion criteria of which 365 (62.5%) had a microbiological diagnosis. MSSA was the most common pathogen identified (45.5%) followed by MRSA (31.2%). The percentage of MRSA cases decreased by 25.4% between 2009 and 2016, whereas MSSA infections increased by 18.6%. Compared to MSSA, patients with MRSA had a higher initial C-reactive protein (median 17.3 mg/dL vs 7.8 mg/dL, p<0.05) and a longer hospitalization (median 8.3 days vs 6.1 days, p<0.05). Patients whose initial antibiotic regimens included vancomycin were more likely to require a PICU transfer (15.0% vs 2.2%, p<0.05) and had a longer hospitalization (median 6.7 days vs 5.5 days, p<0.05) compared to those initiated on clindamycin without vancomycin.CONCLUSIONS While MRSA was associated with increased severity of osteoarticular infections compared to MSSA, the incidence of MRSA has been declining at our institution. Patients with longer lengths of stay and those requiring a PICU transfer were more likely to be on vancomycin. Clindamycin should be considered in the initial antibiotic regimen for osteomyelitis and septic arthritis with ongoing surveillance of local microbiology and outcomes.