The aim of this study was to evaluate the long-term risk of atrial fibrillation (AF) and stroke in patients with atrial septal defect (ASD) diagnosed before the age of 18 years. Patients diagnosed with ASD from 1963 to 2011 were identified through national Danish registers, of which 1,111 fulfilled the inclusion criteria. Each patient was matched with 10 control subjects on age and gender. Risk of AF and stroke was assessed using Cox proportional hazards regression. Cumulative incidences were calculated using Fine and Gray competing risk regression. Median follow-up time was 24 years (range 1 to 49 years). Patients with ASD had a significantly increased risk of AF; both with closure (adjusted hazard ratio [HR] 18.5, 95% confidence interval [CI] 7.8 to 44.1, p <0.0001) and without closure (HR 16.4, 95% CI 6.8 to 39.8, p <0.0001) were compared with control subjects. A comparison of surgical closure with transcatheter closure showed no difference in risk of AF (HR 1.1, 95% CI 0.3 to 4.8, p = 0.864). Risk of stroke was increased in patients with ASD closure (adjusted HR 5.0, 95% CI 2.3 to 11.1, p <0.0001) compared to the control subjects. The use of anticoagulants was increased in patients with ASD regardless of closure (adjusted HR 7.7, 95% CI 4.9 to 12.1, p <0.0001 with closure and HR 4.0, 95% CI 1.9 to 8.7, p <0.0001 without closure). Usage of antiarrhythmic drugs was significantly increased in patients with ASD with closure (adjusted HR 14.8, 95% CI 7.2 to 30.2, p <0.0001). In conclusion, patients diagnosed with an ASD before the age of 18 years had an increased risk of AF in adulthood compared to controls. The risk of AF and stroke was increased despite closure in childhood, and method of closure did not affect the risk of developing AF later in life.