228 patients scheduled for total knee or hip arthroplasty and identified as Staphylococcus aureus (S. aureus) carriers upon preoperative screening were randomized to a preoperative nasal decolonization protocol in addition to standard antibiotic prophyalaxis, or standard prophylaxis alone. The purpose of this randomized trial was to evaluate the efficacy of the preoperative decolonization protocol in reducing infection rate postoperatively. An additional 800 patients who were identified as noncarriers upon screening were assessed to estimate the prevalence of S. aureus carriers among patients undergoing total joint arthroplasty, and the incidence of postoperative infection. The results of the randomized cohorts demonstrated no significant differences in infection rates between groups postoperatively.