Adequate management of wounds requires numerous interventions, one of which is the appropriate use of antimicrobials to attempt to minimize the risk of excess morbidity or mortality without increasing toxicity or multidrug resistant bacterial acquisition. There are numerous recommendations and opinions for not only the use of systemic prophylactic antimicrobials, but also the agent, dose, route, and duration. To best address the implementation of systemic antimicrobials in a field scenario, one must weigh the factors that go into that decision and then determine the best agents possible. The epidemiologic triangle (ie, the host, the agent, and the environment) forms the basis for selecting the correct prophylactic antibiotic for field wound care. Extreme conditions can be encountered in both military and nonmilitary systems, requiring a unique selection process to make the right antibiotic choice. A modifiable weighted matrix, recommended previously for point of injury combat casualty care, assists in selecting the best oral and intravenous/intramuscular agent based on the epidemiologic risk determination.