Background: Undetected clinical deterioration is a major cause of high mortality events in Emergency Department (ED) patients. Yet, there is no known model to guide the recognition and response to clinical deterioration in the ED, integrating internal and external resources. Methods: An integrative review was firstly conducted to identify the critical components of recognising and responding to clinical deterioration in the ED. Components identified from the review were analysed by clinical experts and informed the development of an ED Clinical Emergency Response System (EDCERS). Results: Twenty four eligible studies were included in the review. Eight core components were identified: 1) vital sign monitoring; 2) track and trigger system; 3) communication plan; 4) response time; 5) emergency nurse response; 6) emergency physician response; 7) critical care team response; and 8) specialty team response. These components informed the development of the EDCERS protocol, integrating responses from staff internal and external to the ED. Conclusions: EDCERS was based on the best available evidence and considered the cultural context of care. Future research is needed to determine the useability and impact of EDCERS on patient and health outcomes.