The primary aim of our investigation was to describe the safety and feasibility of a protocol for prehospital recognition of sepsis with hypotension and septic shock, drawing of blood cultures, and administration of intravenous (IV) antibiotics in an urban EMS service, thereby adding to the limited U.S. literature available on this subject and supporting the development of a large-scale randomized control trial (RCT). Primary feasibility measures included the frequency of allergic reactions, culture contamination, and paramedic adherence to the protocol in the prehospital environment.