Background: Open penetrating trauma wounds to the extremities remain the most common injuries encountered in combat and are frequently complicated by bacterial infections. These infections place a heavy burden on the Servicemember and the healthcare system as they often require multiple additional procedures and can frequently cause substantial debility. Previous studies have shown that vancomycin powder has demonstrated efficacy in decreasing infection risks in clean and contaminated orthopedic surgical wounds. Methods: This review evaluates the most prevalent organisms cultured post-trauma, the current Tactical Combat Casualty Care (TCCC) guidelines for antibiotic prophylaxis, and relevant research of vancomycin's prophylactic use. Results: Results from previous studies have shown a time-dependent reduction in bacterial load when vancomycin powder is introduced early post injury in traumatic orthopedic wounds. Furthermore, perioperative application affords a cost-effective method to prevent infection with minimal adverse effects. Discussion: The current TCCC guidelines advocate for the use of antibiotics at the point of injury. When vancomycin powder is used in synergy with these guidelines, it can contribute a timely and powerful antibiotic to prevent infection. Conclusion: The prophylactic use of vancomycin powder is a promising adjunctive agent to current Clinical Practice Guidelines (CPG), but it cannot be conclusively determined to be effective without further research into its application in traumatic combat wounds.