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Although Staphylococcus epidermidis is a frequent cause of prosthetic valve endocarditis (PVE), it is regarded as a rare pathogen of native valve endocarditis (NVE). We report a case of NVE caused by methicillin-resistant S. epidermidis in a 62-year-old man. The bacterium was isolated from blood and tissue culture. The patient underwent valve replacement due to heart failure and was successfully treated by surgery and vancomycin administration for 7 weeks.