Background: Deep incisional surgical site infection (SSI) is a devastating and costly complication of primary total knee arthroplasty (TKA). The effectiveness of antibiotic-loaded bone cement (ALBC) in preventing these infections remains controversial. Methods: A meta-analysis was conducted to assess the efficacy of ALBC in preventing deep infection in primary TKA after a detailed and systematic search of the PubMed, Embase, CNKI, and Cochrane databases had been performed to identify appropriate comparative trials on the prophylactic use of ALBC in primary TKA. Results: Five comparative trials were included. In total, 3,461 patients (ALBC group) received ALBC, whereas 3,176 patients (non-antibiotic-loaded cement; NALBC group) did not. The incidence of deep incisional SSI in the ALBC group was 1.32% (n=46) whereas the incidence in the NALBC group was 1.89% (n=60), figures which are not significantly different. No adverse events associated with ALBC were reported in any studies. Conclusion: Statistical analysis did not reveal a significantly different incidence of deep or superficial SSI in patients receiving and not receiving antibiotic-loaded cement. The prophylactic application of ALBC thus did not show efficacy in primary TKA. More large-sample studies are required to confirm this finding.