Prosthetic joint infection (PJI), although uncommon, is a dreaded and devastating complication of total hip replacement (THR). Whether implant-related factors, such as the fixation method, influences the risk of PJI following THR is contentious. We conducted a systematic review and meta-analysis to evaluate the body of evidence linking fixation methods (cemented, uncemented, hybrid, or reverse hybrid) with the risk of PJI following primary THR. Observational studies and randomised controlled trials (RCTs) comparing fixation methods, and reporting PJI incidence following THR, were identified through MEDLINE, Embase, Web of Science, Cochrane Library, and reference lists of relevant studies up to 24 April 2019. Summary measures were relative risks (RRs) (95% confidence intervals, CIs). We identified 22 eligible articles (based on 11 distinct observational cohort studies comprising 2,260,428 THRs and 4 RCTs comprising 945 THRs). In pooled analyses of observational studies, all cemented fixations (plain and antibiotic combined), plain cemented fixations, hybrid fixations, and reverse hybrid fixations were each associated with an increased overall PJI risk when compared with uncemented fixations: 1.10 (95% CI: 1.04–1.17), 1.50 (95% CI: 1.27–1.77), 1.49 (95% CI: 1.36–1.64), and 1.49 (95% CI: 1.14–1.95), respectively. However, in the first six months, uncemented fixations were associated with increased PJI risk when compared to all cemented fixations. Compared to antibiotic-loaded cemented fixations, plain cemented fixations were associated with an increased PJI risk (1.52; 95% CI: 1.36–1.70). One RCT showed an increased PJI risk comparing plain cemented fixations with antibiotic-loaded cemented fixations. Uncemented and antibiotic-loaded cemented fixations remain options for the prevention of PJI in primary THR.