To develop an evidence-driven, behaviour change focused strategy to maximise implementation and uptake of HIRAID (History including Infection risk, Red flags, Assessment, Interventions, Diagnostics, communication and reassessment) in 30 Australian rural, regional and metropolitan emergency departments. An embedded, mixed-methods study. This study is the first phase of a step-wedge cluster randomised control trial of HIRAID involving over 1300 emergency nurses. Concurrent quantitative and qualitative data were collected via an electronic survey sent to all nurses to identify preliminary barriers and enablers to HIRAID implementation. The survey was informed by the Theoretical Domains Framework, which is a synthesis of behavioural change theories that applies the science of intervention implementation in health care to effect change. Quantitative data were analysed using descriptive statistics and qualitative data with inductive content analysis. Data were then integrated to generate barriers and enablers to HIRAID implementation which were mapped to the Theoretical Domains Framework. Corresponding intervention functions and Behaviour Change techniques were selected and an overarching implementation strategy was developed through stakeholder consultation and application of the APEASE criteria (Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects/safety and Equity). Six barriers to HIRAID implementation were identified by 670 respondents (response rate ~58%) representing all 30 sites: (i) lack of knowledge about HIRAID; (ii) high workload, (iii) lack of belief anything would change; (iv) not suitable for workplace; (v), uncertainty about what to do and (vi) lack of support or time for education. The three enablers were as follows: (i) willingness to learn and adopt something new; (ii) recognition of the need for something new and (iii) wanting to do what is best for patient care. The 10 corresponding domains were mapped to seven intervention functions, 21 behaviour change techniques and 45 mechanisms. The major components of the implementation strategy were a scaffolded education programme, clinical support and environmental modifications. A systematic process guided by the behaviour change wheel resulted in the generation of a multifaceted implementation strategy to implement HIRAID across rural, regional and metropolitan emergency departments. Implementation fidelity, reach and impact now require evaluation. HIRAID emergency nursing assessment framework reduced clinical deterioration relating to emergency care and improved self-confidence and documentation in emergency departments in pilot studies. Successful implementation of any intervention in the emergency department is notoriously difficult due to workload unpredictability, the undifferentiated nature of patients and high staff turnover. Key barriers and enablers were identified, and a successful implementation strategy was developed. This study uses theoretical frameworks to identify barriers and enablers to develop a data-driven, behavioural-focused implementation strategy to optimise the uptake of HIRAID in geographically diverse emergency departments which can be used to inform future implementation efforts involving emergency nurses. The CROSS reporting method (Supporting Information S3) was used to adhere to EQUATOR guidelines. No Patient or Public Contribution. Australian New Zealand; Clinical Trials Registry (ANZCTR) number: ACTRN12621001456842, registered 25/10/2021.