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The treatment of staphylococcal prosthetic joint infection (PJI) with debridement, antibiotics, and retention of the implant (DAIR) often results in failure. An important evidence gap concerns the treatment with rifampicin for PJI. A systematic review and meta-analysis were conducted to assess the outcome of staphylococcal hip and/or knee PJI after DAIR, focused on the role of rifampicin. Studies published until September 2, 2020 were included. Success rates were stratified for type of joint and type of micro-organism. Sixty-four studies were included. The pooled risk ratio for rifampicin effectiveness was 1.10 (95% confidence interval, 1.00–1.22). The pooled success rate was 69% for Staphylococcus aureus hip PJI, 54% for S aureus knee PJI, 83% for coagulase-negative staphylococci (CNS) hip PJI, and 73% for CNS knee PJI. Success rates for MRSA PJI (58%) were similar to MSSA PJI (60%). The meta-analysis indicates that rifampicin may only prevent a small fraction of all treatment failures. [ABSTRACT FROM AUTHOR]