BackgroundDespite its limitations, a culture remains the “gold standard” for pathogen identification in patients who have periprosthetic joint infection (PJI). Recently, a synovial fluid antigen test has been introduced by a commercial entity. The purpose of this multicenter study was to determine the accuracy of the antigen test in the diagnosis of PJI. MethodsThis retrospective study identified 613 patients undergoing revision total knee arthroplasty who had undergone preoperative synovial fluid analysis. A PJI was defined using the 2018 International Consensus Meeting (ICM) criteria. Patients who had an extended period (> 180 days) from aspiration to revision procedure (n = 62), those presenting within 90 days of their index arthroplasty procedure (n = 17), and patients who had an inconclusive ICM score (n = 8) were excluded. Using receiver operator characteristic curve analyses, we examined the utility of the microbial identification (MID) antigen test and any positive culture (either preoperative or intraoperative) in the diagnosis of PJI. ResultsA total of 526 patients were included. Of these, 125 (23.8%) were ICM positive and 401 (76.2%) were ICM negative. Culture demonstrated an area under the curve (AUC) of 0.864, sensitivity of 75.2%, and specificity of 97.5%. On the other hand, the MID test exhibited an AUC of 0.802, sensitivity of 61.6%, and specificity of 98.8%. The AUC of culture was significantly higher than that of the MID test (P = .037). The MID test was positive in 41.9% of culture-negative PJI cases. We also observed a high rate of discordance (29.7%) when both culture and the MID test were positive in the ICM-positive group. ConclusionsSynovial fluid antigen testing does not provide additional clinical benefit when compared to traditional cultures for the diagnosis of PJI. The antigen test had low sensitivity in the diagnosis of PJI and a relatively high rate of discordance with culture. Level of EvidenceLevel III.