This systematic literature review surveyed the evidence for the acceptability and effectiveness of CBT and psychologically based interventions for emergency department (ED) attenders with physical health complaints as their primary concern, in light of over-burdened EDs and the existing evidence base for psychological interventions in other medical settings. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018087860). A systematic search of three databases (APAPsychNet, Cochrane and PubMed) was performed to identify psychological treatment studies targeting physical health problems presenting in the ED, with broad inclusion criteria to capture a coherent understanding of the current knowledge base. A total of 2606 potential studies for inclusion were identified; 45 proceeded to full review. Twenty papers met the full inclusion. Included studies covered four clinical areas: trauma/PTSD-prevention, panic attacks, non-cardiac chest-pain and miscellaneous. A narrative description of findings reflected positive outcomes across all groups, but this was not consistent across any group. Few studies measured ED attendance (20%) or satisfaction/acceptability (10%). The majority of studies (90%) were underpinned by a cognitive behavioural framework, consistent with the current evidence base as applied to the management of medical conditions. Findings suggest there is some evidence that interventions in the ED are effective and acceptable to patients, but interpretation of findings is limited by the mixed quality of designs and risk of bias. Key learning aims (1) To understand the current body of evidence for the feasibility and effectiveness of psychological interventions in the emergency department. (2) To gain a clear understanding of the models and format of the delivery of CBT and psychological interventions in an acute setting. (3) To identify gaps in the evidence to inform future development of CBT-based interventions to improve outcomes and clinical care.