For patient and personnel safety, agitated and violent individuals are sometime physically restrained during out-of-hospital ambulance transport. We report two cases of unexpected death in restrained, agitated individuals while they were being trans-ported by advanced life support ambulance. Both patients had been placed in hobble restraints by law enforcement. At autopsy, toxicologic analysis revealed nonlethal levels of amphetamines in one patient and nonlethal levels of ethanol, cocaine, and amphetamines in the other. In both cases the cause of death was determined to be positional asphyxiation during restraint for excited delirium. Physicians and emergency service personnel should be aware of the potential complications of using physical restraints for control of agitated patients.