Guidelines have suggested screening for atrial fibrillation to enable early treatment and avoid downstream negative clinical events. We aimed to determine if atrial fibrillation screening potentially enhanced by NT-proBNP would reduce stroke or systemic embolism incidence as compared to in a control group and to determine if it was safe for those with low NT-proBNP concentrations to forfeit prolonged screening. In this randomized controlled trial all 75/76-year-old individuals in Stockholm Region, Sweden were randomized 1:1 to be invited to screening or serve as a control group. NT-proBNP concentration were measured and a single-lead-ECG registered only once if NT-proBNP<125ng/L, whereas if NT-proBNP≥125 ng/L participants underwent prolonged screening, recording single-lead ECGs four times daily for two weeks. If atrial fibrillation was detected, treatment was initiated. Baseline and outcome data were collected from Swedish National Registries. In total 28,712 individuals were randomized, after exclusion of death and emigration 13,905 remained in the intervention group, 13,884 in the control group. Participation rate in the intervention group was 49.2% (6,843/13,905). Participants in the high NT-proBNP group (NT-proBNP≥125 ng/L) without prior atrial fibrillation constituted 60% of the total and underwent prolonged screening. New AF was detected in 2.4% (165/6,843) in the intervention group. There was no difference in AF prevalence or oral anticoagulant treatment between the intervention and the control group after five years follow-up. After a median of 5.1 years (IQR 5.0-5.8) there was no difference in the primary outcome of stroke or systemic embolism between the intervention group and the control group, HR: 0.96 (95% CI 0.86-1.06). The low NT-proBNP-group had significantly fewer strokes or systemic emboli than the control group, HR: 0.59 (95% CI 0.46-0.74), p<0.001. In the high NT-proBNP group the risk of stroke or systemic embolism was higher compared to the low NT-proBNP group, HR: 1.57 (95% CI 1.22-2.02), p=0.001. In this population-based screening trial for atrial fibrillation using NT-proBNP for screening enhancement, there was no difference in risk of stroke or systemic embolism for the intervention group compared to controls. Participation was moderate. The use of NT-proBNP for screening enhancement was safe in identifying low-risk participants. www.clinicaltrials.gov; NCT02743416.