Four thousand two hundred thirty-nine patients undergoing joint replacement surgery were randomized to receive either vancomycin plus cefazolin (n=2044) or cefazolin plus placebo (n=2069). The primary outcome was the incidence of surgical site infections within 90 days. Secondary outcomes included hypersensitivity reactions, acute kidney injury, and other adverse events. Outcomes were assessed up to 90 days post-surgery. Overall, the results of the study revealed that surgical-site infections occurred in 4.5% of the vancomycin group and 3.5% of the placebo group, with a relative risk of 1.28 (P=0.11). Adverse events, including hypersensitivity and acute kidney injury, were similar between groups, with the exception of a higher rate of hypersensitivity reactions in the vancomycin group. The study concluded that adding vancomycin to cefazolin prophylaxis did not significantly reduce surgical-site infections compared to placebo in patients without MRSA colonization.