Commentary Surgical site infection (SSI) complicates care and worsens outcomes among orthopaedic trauma patients. Despite efforts to reduce postoperative infection in this population, the incidence of SSI remains unacceptably high. The study by the Major Extremity Trauma Research Consortium (METRC) is a randomized investigation into the impact of a high versus low perioperative inspiratory oxygen fraction in reducing SSI among orthopaedic trauma patients considered at high risk for infection based on their injury characteristics. The authors should be commended for completing a rigorous investigation of this perioperative intervention. The study was well designed and required a high degree of coordination, and the authors have expertly communicated their results. This multidisciplinary and multicenter collaboration stands as an example to be emulated. Generally, SSI risk can be mitigated through interventions such as perioperative patient optimization, efficient and meticulous surgical technique, appropriate perioperative antibiotics, and the avoidance of autologous blood transfusion when possible. However, given the deleterious effect of infection on treatment outcomes, the search continues for discrete interventions that can further reduce infection risk. Ideal interventions would also be cost-effective and easily scalable to permit expedient widespread implementation. Perioperative supplemental oxygen is a particularly appealing candidate for prophylaxis against infection as it is relatively safe, inexpensive, and ubiquitous. The study results generally favor the perioperative use of a high fraction of inspired oxygen in the treatment of high-risk orthopaedic trauma, although the authors note that the apparent benefit of the intervention was primarily driven by a reduction in superficial infections. Reliably defining superficial infection is inherently difficult as it primarily relies on clinical evaluation. The authors employed a practical method, defining superficial infection by antibiotic administration prompted by a concerning wound evaluation. However, antibiotic administration does not confirm the presence of an infection. For example, a moderately ischemic but uninfected wound may trigger some providers to prescribe antibiotics while others would continue close surveillance or institute other wound-care interventions. Nevertheless, whether the reduction in antibiotic administration in the intervention group was entirely related to the reduction in superficial infection or was more broadly related to improved perfusion and the subjective appearance of wounds, the results suggest that supplemental oxygen has a beneficial effect on wound healing. It is inherently more difficult to demonstrate that an intervention reduces the rate of deep infection, and it is common to employ a combined outcome of superficial and deep infection in research. Given deep infection rates of 5.6% and 6.6% in the treatment and control groups, respectively, a massive study population would be required to appropriately power an investigation into a potential 1% difference in deep infection. However, there is considerable benefit to preventing 1 patient in 100 from developing a deep SSI, and the results of this study generate optimism that such an effect could exist with this low-cost intervention. As discussed above, relatively few discrete interventions have been demonstrated to reduce the rate of SSI in orthopaedic trauma. Identifying interventions that safely contribute to improved wound healing and infection risk is critical to optimizing care. Candidate interventions should be iteratively introduced into established protocols and monitored for their effect on outcomes and interaction with other aspects of care. This study’s results support the consideration of augmenting standard perioperative protocols with high perioperative oxygen supplementation for high-risk cases given its safety, low cost, and availability.