Infections following fracture fixation surgery can be devastating, leading to the need for multiple surgeries and possibly amputation in some cases. It is important to understand which strategies, if any, can help reduce the rate of infection in fracture surgery. The authors in this study performed a pre-planned secondary analysis of the VANCO trial. In this secondary analysis, only patients with infections were analyzed. Patients in the treatment arm (vancomycin powder) with an infection (n = 29) were compared to those with an infection in the placebo group (n = 45). Patients in the vancomycin group were less likely to have Gram-positive bacterial infections, including fewer Methicillin Resistant Staph Aureus (MRSA) and Coagulase Negative Staph (CONS) infections. Thus, vancomycin powder, in addition to reducing overall infection rates, may also selectively have a greater impact on gram positive infections.