Prosthetic joint infections cause serious morbidity and mortality among joint arthroplasty patients. Rifampin-accompanied antibiotic regimens are recommended for gram-positive infections. This study aimed to combine current evidence supporting the rifampin supplement to an effective antibiotic in the treatment of prosthetic joint infections. We conducted a random-effects meta-analysis with frequentist and Bayesian approaches. A total of 13 studies, all observational, were included in the final analysis. The predominant bacteria in eight, two, and three studies were Staphylococcus spp., Propionibacterium spp., and Streptococcus spp., respectively. We pooled data from 568 patients in the staphylococcus subset (OR, 1.18; 95% CIs, [0.76; 1.82]; I-2 = 23%) and data from 80 patients in the propionibacterium subset (REM OR, 1.61; 95% CIs [0.58; 4.47]; I-2 = 0%). Both were insignificant with little heterogeneity. We pooled data from 483 patients in the streptococcus subset; the pooled estimate in this subset favored the use of rifampin supplemented regimens (1.84; [0.90; 3.76]) with moderate to high unaccounted heterogeneity (I-2 = 57%). Bayesian random-effects models produced a posterior probability density indicating that future studies will not favor rifampin supplementation in Staphylococcus infections (mu, 0.074; tau, 0.570; 89% HPD, [- 0.48; 0.54]). Bayesian posterior distribution in the Streptococcus subset displayed a tendency toward rifampin supplementation. Studies had a substantial selection bias. Available evidence did not encourage rifampin-accompanied regimens for staphylococcal infections.