Benzodiazepine and sedative hypnotics (BSHs) incur significant adverse effects and costs, especially in older adults. Addressing BSH overuse in older adults is therefore an urgent priority to improve patient safety in Europe. However, previous attempts did not lead to large-scale reduction in use. The goal of BE-SAFE is to improve patient safety by addressing knowledge and practice gaps related to the reduction of BSHs used for sleep difficulties in Europe. BE-SAFE proposes an interdisciplinary and inter-sectorial approach with experts in guidelines, implementation, dissemination, case studies, geriatrics and sleep. BE-SAFE will emphasize patient involvement by establishing a Patient Partnership Advisory Council with patients, informal carers and patient organisations, which will advise on all aspects of the project. BE-SAFE will conduct a survey among patients, informal carers and healthcare professionals (HCPs) to identify barriers and enablers to BSH reduction. The results will inform the development of guidelines, implementation recommendations and patient-centred materials to support self-management. The approach will be tested in a multinational, cluster randomised controlled trial. Case studies conducted in the six countries will inform the development of country-specific and general logic models to facilitate the scale up and spread of the BE-SAFE intervention and adapt inter-sectoral clinical pathways. Finally, BE-SAFE will develop a toolkit to disseminate the new best practices to allow different European healthcare systems to implement this process in a standardised way, while allowing for adaptation to account for country and context differences. BE-SAFE multifaceted patient-centred approach will provide resources for patients, HCPs, healthcare systems and policymakers throughout the diverse European healthcare landscape to reduce BSH use threatening patient safety, and serve as a model to address the reduction of other harmful medications.