Excited delirium syndrome (ExDS) is a medical emergency usually presenting first in the prehospital environment. Untreated ExDS is associated with a high mortality rate and is gaining recognition within organized medicine as an emerging public safety problem. It is highly associated with male gender, middle age, chronic illicit stimulant abuse, and mental illness. Management of ExDS often begins in the field when first responders, law enforcement personnel, and emergency medical services (EMS) personnel respond to requests from witnesses who observe subjects exhibiting bizarre, agitated behavior. Although appropriate prehospital management of subjects with ExDS is still under study, there is increasing awareness of the danger of untreated ExDS, and the danger associated with the need for subject restraint, whether physical or chemical. We describe two ExDS patients who were successfully chemically restrained with ketamine in the prehospital environment, and who had good outcomes without complication. These are among the first case reports in the literature of ExDS survival without complication using this novel prehospital sedation management protocol. This strategy bears further study and surveillance by the prehospital care community for evaluation of side effects and unintended complications.