ABSTRACT: The diagnostic potential of D-dimer and fibrinogen to detect periprosthetic joint infection (PJI) of the hip and knee is not well-understood. The aim of this study was to determine whether D-Dimer and fibrinogen can be used as effective biomarkers to screen PJI. A systematic review of the literature indexed in Web of Science, PubMed, Cochrane Library, Embase, and Google Scholar databases was performed. All studies using D-dimer levels in serum or plasma, or fibrinogen levels in plasma, for the diagnosis of PJI were included. Meta-analysis estimates, including sensitivity, specificity, diagnostic odds ratios (DOR), and the area under the summary receiver operating characteristic curve (AUSROC), were calculated using a random-effects model, and used to assess the diagnostic accuracy of these biomarkers. A total of nine studies were analyzed, and their quality was considered to be acceptable. D-dimer gave a limited diagnostic value if serum and plasma combined: sensitivity (0.77, 95% confidence interval [CI] [0.63 to 0.87]), specificity (0.67, 95% CI [0.54 to 0.78]), DOR (6.81, 95% CI [2.67 to 17.37]), and AUSROC (0.78, 95% CI [0.74 to 0.82]). Plasma D-dimer levels were associated with less satisfactory sensitivity (0.65, 95% CI 0.57 to 0.71), specificity (0.58, 95% CI 0.50 to 0.66), DOR (2.52, 95% CI 1.64 to 3.90), and AUSROC (0.65, 95% CI 0.61 to 0.69). Serum D-dimer levels showed higher corresponding values of 0.89 (95% CI 0.79 to 0.94), 0.76 (95% CI 0.55 to 0.89), 24.24 (95% CI 10.07 to 58.32), and 0.91 (95% CI 0.88 to 0.93). Plasma fibrinogen showed acceptable corresponding values of 0.79 (95% CI 0.70 to 0.85), 0.73 (95% CI 0.57 to 0.85), 10.14 (95% CI 6.16 to 16.70), and 0.83 (95% CI 0.79 to 0.86). Serum D-dimer may be an effective marker for the diagnosis of PJI in hip and knee arthroplasty patients, and it may show higher diagnostic potential than plasma fibrinogen. Plasma D-dimer may have limited diagnostic potential.