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Background: Overprescribing of antibiotics is a major concern as it contributes to antimicrobial resistance. Research has found highly variable antibiotic prescribing in (UK) primary care, and to support more effective stewardship, the BRIT Project (Building Rapid Interventions to optimise prescribing) is implementing an eHealth Knowledge Support System. This will provide unique individualised analytics information to clinicians and patients at the point of care. The objective of the current study was to gauge the acceptability of the system to prescribing healthcare professionals and highlight factors to maximise intervention uptake., Methods: Two mixed-method co-design workshops were held online with primary care prescribing healthcare professionals (n = 16). Usefulness ratings of example features were collected using online polls and online whiteboards. Verbal discussion and textual comments were analysed thematically using inductive (participant-centred) and deductive perspectives (using the Theoretical Framework of Acceptability)., Results: Hierarchical thematic coding generated three overarching themes relevant to intervention use and development. Clinician concerns (focal issues) were safe prescribing, accessible information, autonomy, avoiding duplication, technical issues and time. Requirements were ease and efficiency of use, integration of systems, patient-centeredness, personalisation, and training. Important features of the system included extraction of pertinent information from patient records (such as antibiotic prescribing history), recommended actions, personalised treatment, risk indicators and electronic patient communication leaflets. Anticipated acceptability and intention to use the knowledge support system was moderate to high. Time was identified as a focal cost/ burden, but this would be outweighed if the system improved patient outcomes and increased prescribing confidence., Conclusion: Clinicians anticipate that an eHealth knowledge support system will be a useful and acceptable way to optimise antibiotic prescribing at the point of care. The mixed method workshop highlighted issues to assist person-centred eHealth intervention development, such as the value of communicating patient outcomes. Important features were identified including the ability to efficiently extract and summarise pertinent information from the patient records, provide explainable and transparent risk information, and personalised information to support patient communication. The Theoretical Framework of Acceptability enabled structured, theoretically sound feedback and creation of a profile to benchmark future evaluations. This may encourage a consistent user-focused approach to guide future eHealth intervention development., (© 2023. The Author(s).)