AIMS: Screening for atrial fibrillation (AF) is recommended by the European Society of Cardiology guideline to prevent strokes. Cost-effectiveness analyses of different screening programs for AF are difficult to compare, because of varying settings and models used. We compared the impact and cost-effectiveness of various AF screening programs in the Netherlands. METHODS AND RESULTS: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the ARISTOTLE, RE-LY and ROCKET AF trial combined with Dutch observational data. Univariate, probabilistic sensitivity and various scenario analyses were performed. The maximum number of newly detected AF patients in The Netherlands ranged from 4554 to 39 270, depending on the screening strategy used. Adequate treatment with anticoagulation would result in a maximum of more than 3000 strokes prevented using single time point AF screening. Compared with no screening, screening 100 000 persons provided a gain in QALYs ranging from 984 to 8727, and a mean cost difference ranging from -6650 000€ to 898 000€, depending on the screening strategy used. Probabilistic sensitivity analysis (PSA) demonstrated a 100% likelihood that screening all patients ≥ 75 years visiting the Geriatric outpatient clinic was cost-saving. Four out of six strategies were cost-saving in ≥ 74% of the PSA simulations. Out of these, opportunistic screening of all patients ≥ 65 years visiting the GPs office had the highest impact on strokes prevented. CONCLUSION: Most single-time point AF screening strategies are cost-saving and have an important impact on stroke prevention.