Summary: The purpose of this study is to conduct a meta-analysis to evaluate the efficacy of screening and decolonization protocol for Staphylococcus aureus (SA) in total joint arthroplasty (TJA). We systematically searched the electronic databases of PubMed, Embase and Cochrane databases for relevant literatures from January 2000 to September 2020. The outcomes were colonization rate, total-surgical site infection (SSI) rate, SA-SSI rate and methicillin-resistant Staphylococcus aureus (MRSA)-SSI rate. All calculations and statistical tests were performed using Stata 14.0 software. A total of 12 studies were eligible in this study. Compared with control group, the screening and decolonization group had lower risks in total-SSI (risk ratio (RR) = 0.52; 95% confidence interval (CI): 0.40–0.67), SA-SSI (RR = 0.48; 95% CI: 0.32–0.72) and MRSA-SSI (RR = 0.45; 95% CI: 0.21–0.96). The nasal SA colonization was found to be associated with higher accidences of SSI involving total-SSI (RR = 1.49; 95% CI: 1.02–2.18), SA-SSI (RR = 2.51; 95% CI: 0.97–6.50) and MRSA-SSI (RR = 7.84; 95% CI: 1.67–36.79). The colonization rate of SA was significantly reduced after decolonization. No difference was observed between universal decolonization and screening-based decolonization. In conclusion, colonization of SA is associated with increased risk of SSI in TJA. Screening and decolonization protocol are proven to be effective to reduce colonization of SA and present protective effects against SSI in TJA. Moreover, universal decolonization protocol is non-inferior to screening-based decolonization.