IntroductionAntimicrobial resistance is a leading global public health threat, with inappropriate use of antimicrobials in healthcare contributing to its development. Given this urgent need, we developed a complex ePrescribing-based Anti-Microbial Stewardship intervention (ePAMS+).Methods and analysisePAMS+ includes educational and organisational behavioural elements, plus guideline-based clinical decision support to aid optimal antimicrobial use in hospital inpatients. ePAMS+ particularly focuses on prompt initiation of antimicrobials, followed by early review once test results are available to facilitate informed decision-making on stopping or switching where appropriate. A mixed-methods feasibility trial of ePAMS+ will take place in two NHS acute hospital care organisations. Qualitative staff interviews and observation of practice will respectively gather staff views on the technical component of ePAMS+ and information on their use of ePAMS+ in routine work. Focus groups will elicit staff and patient views on ePAMS+; one-to-one interviews will discuss antimicrobial stewardship with staff and will record patient experiences of receiving antibiotics and their thoughts on inappropriate prescribing. Qualitative data will be analysed thematically. Fidelity Index development will enable enactment of ePAMS+ to be measure objectively in a subsequent trial assessing the effectiveness of ePAMS+. Quantitative data collection will determine the feasibility of extracting data and deriving key summaries of antimicrobial prescribing; we will quantify variability in the primary outcome, number of antibiotic defined daily doses (DDD), to inform the future larger- scale trial design.Ethics and disseminationThe qualitative research and Fidelity Index were approved by the Health and Research Authority and the North of Scotland Research Ethics Service (ref:19/NS/0174). The feasibility trial and quantitative analysis were approved by the London South East Research Ethics Committee (ref:22/LO/0204). Findings will be shared with study sites and with qualitative research participants and will be published in peer-reviewed journals and presented at academic conferences.Trial registrationISRCTN 13429325 (protocol v1.0, 15/12/2021)Strengths and limitationsMixed-methods study, incorporating qualitative and quantitative elements, assessing feasibility of a trial evaluating the ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention.The feasibility trial will inform refinements of ePAMS+ intervention and its future full-scale evaluation.Development of a Fidelity Index to enable adherence to the ePAMS+ intervention to be assessed objectively.Two study sites may limit generalisability, although inclusion of several ward types will ensure the trial covers a breadth of clinical contexts.Implementation of ePAMS+ in the Cerner ePrescribing and Medicines Administration (EPMA) system means feasibility in other systems will still need to be established.Lay summaryNot all infections are caused by bacteria. For those that are, antibiotics may be a suitable treatment. When patients first come to hospital, it is sometimes not clear what is causing their illness so doctors may prescribe antibiotics just in case until results from tests to identify the presence of microbes are available. The more antibiotics a person takes the more likely they are in the future to develop bacteria in their body that antibiotics are less effective at treating. The ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention is designed to guide the appropriate use of antibiotics. ePAMS+ uses the hospital electronic patient health record to alert prescribers to situations where changing or stopping antibiotics may be a good option for a patient, consistent with existing national guidelines.The ePAMS+ intervention will prompt healthcare professionals responsible for prescribing to review the progress and test results of a patient receiving antibiotics. After such a review:doctors may decide that a patient will need to carry on with antibiotics because they are right for their illness;healthcare staff may receive test results that can inform how long antibiotics should be prescribed for and which are best to treat the infection;patients may have their antibiotics stopped if the prompts alert the prescriber to decide that the illness is not caused by bacteria.By implementing the ePAMS+ intervention in two hospitals and interviewing staff and patients, this study will assess whether ePAMS+ and our implementation methods are acceptable. It will also confirm whether it is possible to gather the data needed to assess how well ePAMS+ works. This will help design a future larger-scale study.