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The aim of this systematic review and meta-analysis was to assess the diagnostic value of the histological analysis of deep tissue samples in the diagnosis of periprosthetic joint infection (PJI) following total hip (THA) or knee arthroplasty (TKA). The efficacy of the most prevalent diagnostic thresholds (≥ 23 polymorphonuclear neutrophils (PMNs)/ten high-power fields (HPFs), ≥ five PMNs/HPF, and ≥ ten PMNs/HPF) was investigated to determine the optimal threshold to differentiate between septic and aseptic cases. A meta-analysis of the 43 included studies determined the pooled sensitivity, specificity, the diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristic curve (AUSROC) of permanent (formalin-fixed) and frozen sections. The threshold of ≥ five PMNs/HPF demonstrated the best diagnostic performance (sensitivity 82.0% (95% CI 80.0 to 84.0), specificity 94.7% (95% CI 93.5 to 95.8), DOR 133.5 (95% CI 41.6 to 428.6), and AUSROC 0.963 (SE 0.02)).