Objective To study the clinical characteristics and virulence gene distribution of Staphylococcus aureus (SA) of different infection types. Methods SA isolated from 11 member hospitals in Baotou which participates the national bacterial resistance monitoring network from January 2018 to December 2020 were collected. Medical records of patients with included strains were analyzed retrospectively, clinical characteristics of infection and antimicrobial resistance were analyzed. The strains were conducted stratified sampling, samples were taken as the tested strains for virulence gene detection. WHONET 5.6 and SPSS 22.0 software were used for data analysis. Results A total of 2 452 SA strains were collected. There were 932 cases of surgical infection, 504 cases of respiratory tract infection, 172 cases of blood stream infection and 844 cases of other types of infection. Patients with SA infection were mainly females (68.23%). There were significant differences in the distribution of infection types among SA infected patients of different gender and age (all P < 0.001). Surgical infection, respiratory tract infection and blood stream infection mainly occurred in patients < 60 years old. Patients with surgical infection had a higher proportion of hospitalization time >2 weeks, accounting for 39.21%. The mortality of patients with SA respiratory tract infection was 76.39%. The levels of white blood cell count, neutrophil count, percentage of neutrophils, platelet count, and prothrombin time in patients with different types of infection were all significantly different (all P < 0.05). There were significant differences in the levels of C-reactive protein, procalcitonin, interleukin-6, D-dimer, and fibrinogen degradation products of patients with different infection types (all P < 0.05). Antimicrobial resis-tance rates of MRSA causing different types of infection to ciprofloxacin, gentamicin, levofloxacin and moxifloxacin were significant (all P < 0.05). Carrying rate of clfa, clfb, scn, coa, nuc, hla, hld were all high in different types of infection (>94), proportion of LukED in surgical infection was higher than that of the other three types of infection, difference was significant (P < 0.05). Conclusion Clinically isolated SA carries more virulence genes and has high toxicity, and there are differences in antimicrobial resistance among different types of SA infection.