A systematic review was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). An in-depth search strategy was devised to identify studies which focused on the ED and CBRNe events. The inclusion criteria were stringent in terms of the environment (ED), participants (first receivers), situation (CBRNe response), and actions (detection, decontamination, and diagnosis). Fifteen databases and topic-specific journals were searched. Studies were critically appraised using the Mixed Methods Appraisal Tool (MMAT). Papers were thematically coded and synthesized using NVivo 10 (QSR International Ltd, Melbourne, Australia). Sixty-seven full-text papers were critically appraised using the MMAT; 70% were included (n = 60) as medium- or high-quality studies. Data were grouped into four themes: preparedness, response, decontamination, and personal protective equipment (PPE) problems.DiscussionThis study has recognized the ED as a system which depends on four key factors - preparedness, response, decontamination, and PPE problems - which highlight challenges, uncertainties, inconsistencies, and obstacles associated with the ED CBRNe response. This review suggests that response planning and preparation should be considered at three levels: organizational (policies and procedures); technological (decontamination, communication, security, clinical care, and treatment); and individual (willingness to respond, PPE, knowledge, and competence). Finally, this study highlighted that there was a void specific to detection and diagnosis of CBRNe exposure on self-presenting patients in the ED. The review identified concerns for both knowledge and behaviors which suggests that a systems approach would help understand the ED response to CBRNe events more effectively. The four themes provide an evidence-based summary for the state of science in ED CBRNe response, which can be used to inform future policies and clinical procedures. RazakS, HignettS, BarnesJ. Emergency department response to chemical, biological, radiological, nuclear, and explosive events: a systematic review. Prehosp Disaster Med. 2018;33(5):543-549.