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Background: Enterococcal Infective Endocarditis (EIE) is usually treated with the combination of penicillin/ampicillin with gentamicin or ampicillin with ceftriaxone. To enable prolonged outpatient treatment, a combination of benzylpenicillin and ceftriaxone has been suggested. This study aimed to describe the incidence and characteristics of EIE and to determine the outcome of EIE cases treated with benzylpenicillin and ceftriaxone., Methods: This was a retrospective single-center study including all patients diagnosed with infective endocarditis (IE) during 2016-2021, comparing EIE with IE caused by other pathogens. We described the outpatient treatment of patients with EIE, comparing those treated of benzylpenicillin - ceftriaxone with other regimes., Results: Among 222 patients with IE, 44 (20%) were diagnosed with EIE. Those were older, had a male predominance (p = 0.035), and were more disabled (p = 0.004). The incidence of EIE reached 30% towards the last year, becoming the leading etiology. Twenty-six patients received outpatient treatment, five of whom were discharged with benzylpenicillin and ceftriaxone. Adding patients from this cohort to the scarce data available, revealed similar recurrence and mortality rates compared to other treatment regimes., Conclusions: EIE is becoming a more frequent cause of IE, involving older, more disabled patients with male predominance. Our experience and existing literature suggest that the combination of benzylpenicillin and ceftriaxone is as safe as more conventional regimes, although further research is needed., Competing Interests: Declaration of ompeting interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)