Abstract: OBJECTIVE To study Staphylococcus epidermidis infection status and quinolones resistance mechanism of patients with infective endocarditis, so as to provide references for the selection of clinical antibacterial drugs of S. epidermis. METHODS A total of 132 cases patients with infective endocarditis in the hospital from Jan. 2014 to Dec. 2015 were selected. The blood specimens were collected, pathogens were cultured and separated, drug sensitive test was carried, minimum inhibitory concentration (MIC) was determined, drug resistance of S. epidermidis to quinolones were detected, gyrA gene was amplified and sequenced by PCR, and the results were analyzed. RESULTS Totally 36 cases of patients occurred S. epidermidis infection in 123 cases of patients, with the infection rate of 27.27%. The drug resistant rate of S. epidermidis to norfloxacin was 100.00%. The length of PCR amplification of gyrA gene product was 275bp. Some of the strains had multiple-point mutations at the same time. CONCLUSION S. epidermidis is a major pathogen causing infective endocarditis. For the majority of quinolones is widespread drug resistance. Resistant S. epidermidis exists gyrA gene variation. Drug resistant S. epidermidis exists gyrA gene variant, and this may be one of the mechanisms of resistance to quinolones.