Abstract Introduction Benzodiazepine and sedative hypnotics (BSH) may have significant adverse effects and associated costs, especially in older adults: increased risk of falls, fractures, hospitalisations, impaired functioning, delirium, cognitive impairment and mortality. Addressing BSH overuse is therefore an urgent priority to improve patient safety in Europe. Objectives To present the 5-year research project BE-SAFE, funded by the European Commission (HORIZON Europe) and by the Swiss State Secretariat for Education, Research, and Innovation. BE-SAFE aims to improve patient safety by addressing knowledge and practice gaps related to the reduction of BSH used by older adults for sleep problems. Methods BE-SAFE involves seven inter-related work packages and six European countries (Belgium, Greece, Norway, Poland, Spain and Switzerland) as well as experts from Canada; it proposes an interdisciplinary and inter-sectorial approach with experts in guidelines, implementation, dissemination, case studies, geriatrics and sleep. BE-SAFE will develop an intervention comprising trustworthy clinical guidelines, implementation recommendations and patient-centred material. This intervention will be tested in a cluster randomized controlled trial; 470 patients (65 years old and above) and 62 prescribing physicians in hospital and outpatient settings. Results BE-SAFE is expected to result in reduction of BSH use. Its toolkit, encompassing setting-specific implementation recommendations, will enable healthcare professionals (HCPs) to identify, evaluate and prevent risks of BSH use. The BE-SAFE approach could also be expanded to cover reduction of use of other medications. Conclusions Through BE-SAFE, patient safety is expected to improve; BE-SAFE project will reach a wide-ranging audience, including general population, informal carers, older adults, HCPs, healthcare system leaders and decision makers. Authors acknowledge the significant input of J. Grimshaw and W. Levinson, Canada. Key messages • Deprescription of benzodiazepine and sedative hypnotics, especially in older adults, is a priority due to their side effects, particularly in this age group. • The European project BE-SAFE aspires to create easy-to-use guidelines to this aim, improving thus patient safety and healthcare.