There is an increasing incidence of revision for periprosthetic joint infection. The addition of vancomycin to beta-lactam antimicrobial prophylaxis in joint arthroplasty may reduce surgical site infections, however, the efficacy and safety have not been established. This was a multicenter, double-blind, superiority, placebo-controlled trial. We randomized 4239 adult patients undergoing joint arthroplasty surgery to receive 1.5g vancomycin or normal saline placebo, in addition to standard cefazolin antimicrobial prophylaxis. The primary outcome was surgical site infection at 90-days from index surgery. Perioperative carriage of In the 4113 patients included in the modified intention-to-treat population, surgical site infections occurred in 72/2069 (3.5%) in the placebo group and 91/2044 (4. 5%) in the vancomycin group (risk ratio 1.28; 95% confidence interval 0.94 to 1.73; p value 0.11). No difference was observed between the two groups for primary hip arthroplasty procedures. A higher proportion of infections occurred in knee arthroplasty patients in the vancomycin group (63/1109 [4.7%]) compared with the placebo group (42/1124 [3.7%]; risk ratio 1.52; 95% confidence interval 1.04 to 2.23; p value 0.031). Hypersensitivity reactions occurred in 11 (0.5%) patients in the placebo group and 24 (1.2%) in the vancomycin group (risk ratio 2.20; 95% confidence interval 1.08, 4.49) and acute kidney injury in 74 (3.7%) patients in the placebo group and 42 (2.1%) in the vancomycin group (risk ratio 0.57; 95% confidence interval 0.39, 0.83). Perioperative This is the first randomized controlled trial examining the addition of a glycopeptide antimicrobial to standard beta-lactam surgical antimicrobial prophylaxis in joint arthroplasty. The addition of vancomycin to standard cefazolin prophylaxis
