BACKGROUND: Despite numerous tests and guidelines, diagnosing periprosthetic joint infection (PJI) remains challenging. The study aimed to determine the value of synovial D-dimer, rather than serum, in diagnosing PJI. METHODS: This prospective study enrolled 17 patients with chronic knee PJI (the PJI group) and 52 with primary knee osteoarthritis (the control group). PJI was defined using the 2018 International Consensus Meeting Criteria. Synovial D-dimer, plasma D-dimer, serum erythrocyte sedimentation rate, and serum C-reactive protein levels were measured. Synovial fluid D-dimer levels were determined using an enzyme-linked fluorescence assay. The performance of each biomarker in diagnosing PJI was evaluated using receiver operating characteristic (ROC) curves. RESULTS: The median synovial D-dimer level was significantly higher in the PJI group at (927,095 ng/ml, IQR 566,882-1,215,066) than in the control group (20,954 ng/ml, IQR 10,350-46,493) (P <
0.001). When the synovial D-dimer threshold value was determined to be 236,804 ng/ml, the sensitivity was 100% (CI 93.2-100%), and the specificity was 94.12% (95% CI 71.3-99.9). The area under the curve determined by ROC analysis was 0.992 (95% CI 0.992-1.000, P <
0.0001). CONCLUSIONS: Patients with chronic knee PJI have significantly high synovial D-dimer levels, demonstrating that an increase in fibrinolytic activity coexists with an infection-induced inflammatory response. Synovial D-dimer levels appear to be valuable biomarkers for diagnosing PJI. However, further studies are required to evaluate the role of this novel biomarker.