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Introduction In shift work, quick returns refer to transitions between two shifts with less than 11 hours available rest time. Twenty-three per cent of employees in European countries reported having quick returns. Quick returns are related to short sleep duration, fatigue, sleepiness, work-related accidents and sickness absence. The present study is the first randomised controlled trial (RCT) to investigate the effect of a work schedule without quick returns for 6 months, compared with a work schedule that maintains quick returns during the same time frame.Methods and analysis A parallel-group cluster RCT in a target sample of more than 4000 healthcare workers at Haukeland University Hospital in Norway will be conducted. More than 70 hospital units will be assessed for eligibility and randomised to a work schedule without quick returns for 6 months or continue with a schedule that maintains quick returns. The primary outcome is objective records of sickness absence; secondary outcomes are questionnaire data (n≈4000 invited) on sleep and functioning, physical and psychological health, work-related accidents and turnover intention. For a subsample, sleep diaries and objective sleep registrations with radar technology (n≈ 50) will be collected.Ethics and dissemination The study protocol was approved by the Regional Committee for Medical and Health Research Ethics in Western Norway (2020/200386). Findings from the trial will be disseminated in peer-reviewed journals and presented at national and international conferences. Exploratory analyses of potential mediators and moderators will be reported. User-friendly outputs will be disseminated to relevant stakeholders, unions and other relevant societal groups.Trial registration number NCT04693182.