Linezolid and vancomycin are both recommended for the treatment of staphylococcal-associated central nervous system (CNS) infections. However, to date, no data are available comparing the outcomes of patients treated with vancomycin or linezolid for these infections. The aim of this study was to compare the incidence of treatment failure and adverse events (AEs) associated with vancomycin and linezolid in staphylococcal-associated CNS infections. This retrospective monocentric observational study was conducted between 01/01/2015 and 31/12/2023. All patients with a confirmed staphylococcal associated CNS infection and treated with vancomycin or linezolid were included. Failure of antimicrobial treatment was the primary outcome of interest, defined by a composite criteria: persistence of infection (i.e. positive culture after > 72 h of antimicrobial treatment active on the isolated bacteria), relapse of infection (i.e. new infection with the same bacteria involved in the initial episode) or infection related death. Second outcome of interest was AE incidence related to linezolid or vancomycin. Outcomes were analysed using survival analysis techniques and propensity score. Ninety one patients were included: 51 in vancomycin group and 40 in linezolid group. Infections were mainly meningitis (n = 71; 78%). Median duration of linezolid or vancomycin treatment was 7 days (IQR 4; 13). Treatment failure occurred in 18.6% (n = 17) of patients (infection persisted in 9.8% of patients (n = 9), infection relapsed in 6.6% (n = 6) and infection caused a fatal outcome in 4.4% (n = 4). In the Cox proportional hazards regression model, vancomycin was not associated with treatment failure (aHR 2.90; 95% CI [0.93-9.30]; p = 0.066). Using propensity score, vancomycin was associated with treatment failure (HR 3.28; 95% CI [1.02-10.54]; p = 0.045). Treatment with vancomycin was also associated with AE (HR 8.42; CI 95% [2.44;29.10]; p = 0.019). Patients treated with vancomycin for staphylococcal-associated CNS infections seems to have a higher risk of treatment failure and AE compared to those treated with linezolid. However, given the low statistical power and the observational nature of this study, further research is needed to confirm these findings.< Leer menos