Objective To analyze the distribution characteristics of pathogens, antimicrobial resistance and treatment of peri-prosthetic joint infection (PJI) after artificial joint replacement, and provide basis for clinical rational choice of antimicrobial agents. Methods Clinical data of patients with PJI and admitted to a hospital from January 2019 to November 2021 were collected retrospectively, distribution characteristics of pathogens, antimicrobial susceptibility testing results and antimicrobial use of patients were statistically analyzed. Results A total of 96 patients with PJI were included in the study, 112 strains of pathogenic bacteria were isolated, 80.36% of which were Gram-positive strains, mainly Staphylococcus spp.. Antimicrobial susceptibility testing results showed that resistance rate of Staphylococcus epidermidis to penicillin and oxacillin were 96.30% and 81.48% respectively, resistance rates of Escherichia coli to gentamicin, compound sulfamethoxazole and ampicillin were all 100%. Antimicrobial use in PJI patients during hospitalization period was mainly combination, vancomycin combined with meropenem accounted for 26.04%; vancomycin and meropenem were also the main antimicrobial agents artificially added to bone cement. Conclusion The main pathogen of PJI after joint replacement is Staphylococcus epidermidis, which is ge-nerally resistant to penicillin and oxacillin, anti-infection treatment is mainly vancomycin combined with meropenem.