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Introduction Yoga is an emerging exercise choice for people with cystic fibrosis (CF), but evidence of its effect in this population is scarce, with a recent systematic review advocating for further research. Yoga Outcomes Get Assessed in CF (YOGA-CF) is a real-world multicentre randomised controlled trial (RCT) investigating a bespoke CF-specific online 12-week yoga intervention, vers usual care, to determine effectiveness for adults with CF.Methods and analysis A multicentre RCT of adults with CF across the UK. Participants are randomised to usual care or a 12-week online bespoke yoga programme with an expectation of two classes completed weekly. Assessments of lung function, 1 min sit-to-stand, the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and other trial questionnaires are completed preintervention and postintervention (0 and 12 weeks) and after 12 weeks of follow-up (week 24). The primary outcome is the difference in respiratory-related quality of life measured using the CFQ-R before and after yoga/control. Sample size was calculated based on detecting a minimally clinically important difference of 4 for the CFQ-R respiratory domain, with power of 80% and 5% significance level (total target, n=314).Ethics and dissemination Ethics approval gained from the South Yorkshire and Humber Research Ethics Committee (REC) (reference: 23/YH/0270, project ID 303898). Dissemination to involve direct participant feedback and lay webinar, scientific conference presentation and publication in a peer-reviewed journal.Trial registration number NCT06120465.