Background: A third of older people take five or more regular medications (polypharmacy) potentially increasing the risk of side-effects, hospital admission and death. These effects are higher among people living with frailty who lose their in-built reserves and become vulnerable to changes triggered by small events such as a change in medication. National recommendations suggest that medications taken by frail older people should be reviewed annually by their GPs to identify and reduce/stop inappropriate medications (deprescribing).Yet this does not happen routinely due to GPs’ lack of time, increased workloads and worries about stopping medicines. Recent recommendations suggest involving other non-medical prescribers such as practice pharmacists and advanced nurse practitioners (ANPs) in reviewing medications. However, it is unknown how staff could work together most effectively and whether they have any training needs. Aim: This research will investigate how practice-pharmacists, ANPs and GPs could best work together with patients living with frailty to perform regular medication review. Methods The study involves four work packages (WPs). We will review previous literature to identify what makes a successful medication review and how to safely reduce/ stop inappropriate medications (WP1). Interviews with GPs, practice-pharmacists, ANPs, frail older patients and carers will be conducted (WP2). These will discover views about where medication review should take place, the role of each of the involved parties in the process, type of medications that could be deprescribed, staff development and training needs, barriers and facilitators for implementation, and strategies to address these barriers. Information gathered from WP1&2 will be used to develop the intervention: a structured medication review process using pharmacists, ANPs and GPs most effectively and involving frail patients and their families in decisions about medications (WP3). The intervention will be refined further through a series of workshops with service users, clinicians and commissioners. A training programme to implement the intervention and increase staff confidence in reducing/ stopping medications safely will be developed and delivered to GPs, practice-pharmacists and ANPs based on the Polypharmacy Action Learning Sets approach adopted by the Wessex Academic Health Science Network (AHSN) . Finally, we will assess whether itis feasible and acceptable for staff in four GP practices to be trained and to implement the intervention with their patients (WP4). Public Patient Involvement: Three PPI members have been involved in protocol development and refinement and will continue to contribute to the research study by for example being involved in developing research instruments and monitoring recruitment. Dissemination and Impact: Working with colleagues in the Wessex AHSN and local clinical commissioners, we will be able to share our findings and training programme to the wider research and clinical community in Wessex and potentially influence practices and policies both locally and nationally.