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Background: Clinical use of linezolid for the treatment of methicillin-resistant staphylococcus aureus (MRSA) acute hematogenous osteomyelitis (AHO) is still limited by lacking data about clinical outcomes and adverse effects of long-term usage in children. This study aimed to compare the efficacy and safety of linezolid and vancomycin for the treatment of MRSA AHO in children.Methods: This retrospective study was conducted between January 2011 and December 2018 at the Xijing Hospital, Air Force Military Medical University, China, and compared the clinical efficacy and safety of linezolid and vancomycin in children with MRSA AHO. Demographics, clinical features, laboratory tests, susceptibilities of isolates, treatment outcomes, and adverse events were collected. Variables were analyzed by Fisher’s exact test or Mann-Whitney U-test.Results: 17 patients with MRSA AHO were included in this study (6 children received linezolid and 11 children received vancomycin). Statistically significant differenc was observed in the minimum hemoglobin during the treatment between 2 groups [71.0 (IQR 65.0-91.0) vs 102.0 (IQR 91.0-114.0) g/L, P=0.009], and patients in the linezolid group presented higher anemia rate [5 (83.3%) vs 3 (27.3%), P=0.049] than those in the vancomycin group. Conclusions: Although linezolid and vancomycin have no significant difference in efficacy and safety in the treatment of children with MRSA AHO, the incidence rate of anemia was higher during therapy. Children seemed to be more sensitive to the transient bone marrow suppression effect of linezolid in the prolonged use for MRSA AHO.