Objective To survey and analyze the drug resistance of clinical isolated strains of bloodborne infectious staphylococci, in order to provide references for clinical diagnosis of aureus septicemia and rational use of antimicrobial agents. Methods We retrospectively studied the clinical data of 496 patients with staphylococcal septicemia confirmed by blood culture between June 2008 and May 2015 in West China Hospital of Sichuan University. The microbiological characteristics of the disease were analyzed. Results In the included 496 cases, there were 216 (43.55%) cases of coagulase-positive Staphylococcus (CPS) septicemia and 280 (56.45%) of coagulase-negative Staphylococcus (CNS) septicemia; 85 (17.14%) cases were caused by community infection, while the other 411 (82.86%) resulted from hospital infection. The drug resistance rate of CPS and CNS toward oxacillin was respectively 27.78% (60/216) and 87.50% (245/280), with a significant difference (P < 0.05). In al l the clinical isolated strains of CPS, the drug resistance rate of community infected strains and hospital infected strains toward oxacillin was respectively 9.67% (6/62) and 35.06% (54/154), with a significant difference (P < 0.05). For the clinical isolated strains of CNS, the drug resistance rate of community infected strains and hospital infected strains toward oxacillin was respectively 69.57% (16/23) and 89.11% (229/257), also with a significant difference (P < 0.05). Conclusions The drug resistance of hospital infected staphylococcal strains is stronger than community infected strains. The CNS strains are more drug-resistant than CPS strains.