INTRODUCTION: The increasing burden of mental distress reported by healthcare professionals is a matter of serious concern and there is a growing recognition of the role of the workplace in creating this problem. Magnet hospitals, a model shown to attract and retain staff in US research, creates positive work environments that aim to support the well-being of healthcare professionals. METHODS AND ANALYSIS: Magnet4Europe is a cluster randomised controlled trial, with wait list controls, designed to evaluate the effects of organisational redesign, based on the Magnet model, on nurses' and physicians' well-being in general acute care hospitals, using a multicomponent implementation strategy. The study will be conducted in more than 60 general acute care hospitals in Belgium, England, Germany, Ireland, Norway and Sweden. The primary outcome is burnout among nurses and physicians, assessed in longitudinal surveys of nurses and physicians at participating hospitals. Additional data will be collected from them on perceived work environments, patient safety and patient quality of care and will be triangulated with data from medical records, including case mix-adjusted in-hospital mortality. The process of implementation will be evaluated using qualitative data from focus group and key informant interviews. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee Research UZ/KU Leuven, Belgium; additionally, ethics approval is obtained in all other participating countries either through a central or decentral authority. Findings will be disseminated at conferences, through peer-reviewed manuscripts and via social media. TRIAL REGISTRATION NUMBER: ISRCTN10196901.