Introduction: Clinical laboratories offer several multipurpose tests, such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), which are not intended to diagnose any specific disease but are used by clinicians in multiple fields. The results and laboratory interpretation (normal/abnormal) of these multipurpose tests are based on laboratory-reported normal thresholds, which vary across clinical laboratories. In 2018, the International Consensus Meeting on Musculoskeletal Infection (2018 ICM) provided a gold-standard definition to diagnose periprosthetic joint infection (PJI) which included many multipurpose laboratory tests, along with thresholds optimized to diagnose PJI. The discrepancy between laboratory-reported normal thresholds and 2018 ICM-recommended PJI-optimized test thresholds has never been studied. The purpose of this study was to assess the existing variation in laboratory-reported normal thresholds for tests commonly used to diagnose PJI and evaluate the potential diagnostic impact of using laboratory-reported normal thresholds instead of 2018 ICM-recommended PJI-optimized thresholds.Methods: Clinical laboratories (N=85) were surveyed to determine the laboratory-reported units of measure and normal thresholds for common multipurpose tests to diagnose PJI, including the ESR, CRP, D-dimer, synovial fluid white blood cells (SF-WBC), and polymorphonuclear cell percent (SF-PMN%). The variability of units of measure and normal thresholds for each test was then assessed among the 85 included clinical laboratories. A representative dataset from patients awaiting a revision arthroplasty was used to determine the clinical significance of the existing discrepancy between laboratory-reported normal test interpretations and 2018 ICM-recommended PJI-optimized test interpretations.Results: Two units of measure for the CRP and six units of measure for the D-dimer were observed, with only 59% of laboratories reporting the CRP in terms of mg/L and only 16% reporting the D-dimer in ng/ml, as needed to utilize the 2018 ICM definition of PJI. Across clinical laboratories surveyed, the mean laboratory-reported normal thresholds for the ESR (20 mm/h), CRP (7.69 mg/L), D-dimer (500 ng/mL), SF-WBC (5 cells/uL), and SF-PMN% (25%) were substantially lower than the 2018 ICM-recommended PJI-optimized thresholds of 30 mm/h, 10 mg/L, 860 ng/mL, 3,000 cells/uL, and 70%, respectively. Interpretation of test results from a representative PJI dataset using each laboratory’s normal test thresholds yielded mean false-positive rates of 14% (ESR), 18% (CRP), 42% (D-dimer), 93% (SF-WBC), and 36% (SF-PMN%) versus the ICM-recommended PJI-optimized thresholds.Conclusion: When reporting the results for multipurpose laboratory tests, such as the ESR, CRP, D-dimer, SF-WBC, and SF-PMN%, clinical laboratories utilize laboratory-reported units of measure and normal thresholds that are not intended to diagnose PJI, and therefore may not match the 2018 ICM recommendations. Our findings reveal that laboratory-reported normal thresholds for these multipurpose tests are well below the 2018 ICM recommendations to diagnose PJI. Clinical reliance on laboratory-reported results and interpretations, instead of strict use of the 2018 ICM-recommended units and PJI-optimized thresholds, may lead to false-positive interpretation of multipurpose laboratory tests.