Abstract: Background　Periprosthetic joint infection (PJI) represents one of the most catastrophic complications after joint replacement. Since bacterial culture results are often delayed, early treatment is largely dependent on empirical antibiotic therapy. However, substantial discrepancies in pathogen spectra and antimicrobial resistance exist across different regions and institutions, making external data unreliable for formulating local empiric regimens. Objective　To characterize the etiological distribution and resistance patterns to commonly used empiric antibiotics in synovial fluid culture - positive PJI cases in Chinese PLA General Hospital. Methods　A retrospective study was conducted on 214 patients with PJI who were treated in Chinese PLA General Hospital from May 2015 to December 2023. A total of 225 positive synovial fluid culture results were obtained (107 from hips and 118 from knees). Pathogen composition was summarized stratified by hip versus knee. Resistance rates to major antimicrobial agents and the effective coverage rates of commonly used empiric regimens were evaluated. Results　Among the isolates, 180 were Gram-positive bacteria (80%), 27 were Gram-negative bacteria (12.0%), and 16 were fungi (7.1%). The Gram-positive isolates were predominantly Staphylococcus epidermidis (79, 35.1%) and Staphylococcus aureus (32, 14.2%). The Gram-negative isolates were mainly Escherichia coli (9, 4.0%) and Pseudomonas aeruginosa (7, 3.1%). The fungal isolates were primarily Candida parapsilosis (8, 3.6%) and Candida albicans (3, 1.3%). In the knee group (118 isolates), the most common pathogens were S. epidermidis (36, 30.5%), S. aureus (19, 16.1%), and C. parapsilosis (8, 6.8%). In the hip group (107 isolates), S. epidermidis (43, 40.2%), S. aureus (13, 12.1%), and E. coli (8, 7.5%) were the most frequent. The proportion of fungi was higher in the knee group than that in the hip group (12.7% vs 0.9%, P＜001), whereas E. coli was more prevalent in the hip group than that in the knee group (7.5% vs 0.8%, P= 015). Resistance profiling showed that no vancomycin resistance was detected and the resistance rate to linezolid was 1.8% (3/169). The resistance rates to levofloxacin, ciprofloxacin, rifampicin and oxacillin were 36.6% (67/183), 31.6% (55/174), 17.2% (23/134) and 63.9% (76/119), respectively. Among empiric regimens, combination therapies that included Gram-negative coverage achieved the highest effective coverage rates. Conclusion　In this cohort, Gram-positive cocci are the predominant pathogens in PJI and remain susceptible to vancomycin and linezolid; however, relatively high resistance to fluoroquinolones and rifampicin is observed. Fungal infections are more common in knee PJIs than in hip PJIs. Empiric regimens covering Gram-positive organisms while also providing Gram-negative bacillary coverage—such as vancomycin plus meropenem—yield the highest effective coverage rates.