This article describes the SAFER (Screening for Atrial Fibrillation with ECG to Reduce stroke) programme that was established to determine whether intermittent screening for atrial fibrillation with a single-lead electrocardiogram reduces the risk of stroke and other key outcomes such as death, dementia and cardiovascular disease. The programme comprises feasibility studies, a pilot trial, a randomised controlled trial, qualitative studies and an economic analysis. Recruitment and screening for the trial have been completed, and it is anticipated that follow-up will finish in 2027.