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Background: The incidence of Enterococcus faecalis infective endocarditis is increasing over time. Data on the impact of minimum inhibitory concentration (MIC) of amoxicillin on treatment outcomes are scarce. The objective of this study was to describe the epidemiology of E. faecalis infective endocarditis and to evaluate whether the MIC of amoxicillin might influence mortality., Materials: We retrospectively included all consecutive patients diagnosed with definite E. faecalis infective endocarditis between 2013 and 2020 in 11 French hospitals. We extracted data from the local diagnosis-related group (DRG) database and matched these data with microbiological results. Amoxicillin MIC was determined by Etest strip. The primary endpoints were endocarditis-related mortality and risk factors for endocarditis-related mortality including amoxicillin MIC., Results: A total of 403 patients with definite E. faecalis infective endocarditis were included. Patients were predominantly male (76.4%) with a median age of 74 years (67-82). Embolic complications occurred in 170 (42.1%) patients. Cardiac surgery was performed in 158 (61.5%) patients. The endocarditis-related mortality rate was 28.3% and the median delay between mortality and onset of hospitalization was 24 (9; 41) days. E. faecalis MIC of amoxicillin was available for 246 (61%) patients. The median MIC was 0.5 mg/L (0.4-0.7). Amoxicillin MIC was not found to be associated with in-hospital mortality. None of the variables included in the multivariate model were identified as a risk factor for mortality and there was no correlation between mortality and the duration of treatment for 4 weeks versus 6 weeks., Conclusions: Higher amoxicillin MIC was not a risk factor leading to endocarditis-related mortality in definite E. faecalis infective endocarditis. However, further studies are needed to assess the effect of amoxicillin MIC on relapse., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)