BACKGROUND: Despite several markers being evaluated and available in recent years, diagnosing periprosthetic joint infection (PJI) remains challenging. There is a pressing need to explore reliable, economical, convenient, highly sensitive, and specific diagnostic biomarkers to diagnose PJI. This study aimed to investigate the diagnostic value of combined serum markers with CRP and ESR in PJI. METHODS: A total of 841 revision arthroplasty cases, including 435 PJI and 406 non-PJI patients, were enrolled from January 2010 through December 2022. The diagnostic values of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), CRP + ESR (CE), CRP/hemoglobin ratio (CHR), CRP/albumin ratio (CAR), CRP/hemoglobin + albumin ratio (C/HAR), ESR/hemoglobin ratio (EHR), ESR/albumin ratio (EAR), ESR/hemoglobin + albumin ratio (E/HAR), and hemoglobin + albumin (HA) were evaluated using sensitivity, specificity, and receiver operating characteristics analysis with area under the curve (AUC). The optimal threshold was determined using the Youden index. RESULTS: The CHR had the highest AUC (0.87, 95% CI [confidence interval] 0.85 to 0.90) and sensitivity (0.81, 95% CI 0.77 to 0.85) compared to other markers. The CHR exhibited reliable diagnostic adequacy for PJIs caused by low-virulent organisms (sensitivity 0.83, 95% CI 0.76 to 0.89
specificity 0.83, 95% CI 0.79 to 0.86). However, CHR displayed poor sensitivity (0.77, 95% CI 0.67 to 0.86) in patients who have diabetes. CONCLUSIONS: The CHR demonstrated better diagnostic strength in detecting chronic PJI than other classical markers, especially in identifying low-grade infections. Our findings offer new insights into a more accurate and comprehensive picture of pathogens and hosts, thereby improving the accuracy of diagnostic algorithms.