Purpose <p>Despite the high incidence of death among cases of hemorrhagic shock associated with polytrauma, few animal models are representative of this combined type of aggression, as most essentially reproduce soft tissue injury. To improve trauma research and its applicability to battlefield situations, appropriate animal models simulating battlefield trauma care must be defined. As anesthesia itself influences physiological and hemodynamic variables, we studied three different types of anesthesia, ketamine-midazolam (KM), isoflurane (ISO), and alfaxalone (ALFA), in a porcine model of combat-related hemorrhagic shock injury.</p> Methods <p>A total of 19 pigs were randomized to the KM (<i>n</i> = 5), ISO (<i>n</i> = 6), and ALFA (<i>n</i> = 8) groups and subjected to a hemorrhagic shock associated with bilateral femoral fractures and delayed resuscitation.</p> Results <p>The combined traumatic insult with severe hemorrhage resulted in characteristic signs of severe shock. The KM and ISO groups were representative of the hemodynamic perturbation of hemorrhagic shock, whereas the ALFA group showed signs of low tolerance, with extreme and persistent tachycardia even after resuscitation.</p> Conclusions <p>We concluded that ALFA was not the most suitable anesthetic for our hemodynamically compromised model and that KM or ISO were two relevant anesthesia regiments to study traumatic-hemorrhagic shock in pigs. However, KM was the most clinically relevant to medical practices in prehospital medical care or an austere environment.</p>