Human electromuscular incapacitation devices or electromuscular disruption (EMD) devices are increasingly used in police and military applications. Most individuals who experience electromuscular incapacitation are in a stress-filled state, and the effects of prolonged or repeated exposures are not well understood. Three different commercially available EMD devices were tested randomly on 6 anesthetized pigs each for a total of 18 pigs. Each animal was exposed to an initial 60-second application of the EMD device as an initial stressor. The animals were then allowed to rest under anesthesia for 60 minutes followed immediately by a 180-second application of the same device. Arterial blood gases and serum samples were collected throughout the experiment to measure catecholamines (epinephrine, norepinephrine, and dopamine) and cortisol. All the devices produced some level of muscle tetany as a result of the electrical delivery to the animal. All the pigs showed a mixed metabolic and respiratory acidosis. Cortisol tended to decrease after the initial exposure and slightly increased over the rest period. The extreme muscular work caused by the electrical stimulation resulting in muscle contractions did not result in a strong stress response but did result in an immediate sympathetic response during both applications of the device leading to the conclusion that initial stressor followed by rest and prolonged EMD device application did not exhaust the sympathetic system. For healthy adult animals, despite the prolonged muscular exertion and physiological stress caused by EMD devices, the body should be able to mount an appropriate sympathetic response and recover normally.