OBJECTIVES: To determine the cost-effectiveness of primary care screening strategies for atrial fibrillation in England and Wales. METHODS: We built a decision model to compare no screening with opportunistic or systematic screening using 12 permutations of screening tests (modified blood pressure monitors (MBP), photoplethysmography (PP), pulse palpation, or electrocardiograms (ECG)) and interpreters (automatic, nurse, GP, cardiologist). Positive tests at screening were assumed to be confirmed by diagnostic 12-lead ECG interpreted by cardiologist. Long term costs and quality of life for true positive AF cases treated with Apixaban or aspirin were modelled using a Markov model. Model inputs were identified using systematic reviews. We calculated incremental net benefit (INB at £20,000 per QALY), compared to no screening, of screening at ages 55, 60, 65, 70, 75, and 80 and repeat screening strategies with 5-yearly intervals starting at these ages and continuing to age 80. RESULTS: Screening was more cost-effective than no screening. Provided GP uptake is high, opportunistic screening was more likely to be cost-effective than systematic screening. PP (based on one study), MBP and pulse-palpation by a nurse were most likely to be cost-effective. Screening at higher ages was most cost-effective, assuming compliance does not decline with age, with a single opportunistic screen at age 80 having a population INB of £31 (10,62) million. For repeated screening, an initial screen at age 65 followed by 5-yearly repeat screens until age 80 had a probability >60% of being most cost-effective and a population INB of £70 (25, 136) million. CONCLUSIONS: Opportunistic screening of individuals for AF in older adults is likely to be cost-effective, but will require implementation strategies. Screening devices (e.g. MBP, PP) not available in GP practices would require investment if adopted. Investment (approximately £2.2m) would also be required for ECG equipment for the 19% of practices without one.