Low work participation is well known in patients with chronic disease but has not been described in patients with atrial septal defect (ASD). In this nation-wide cohort study, we report the first long-term follow-up of use of permanent social security benefits and work participation in adults with ASD. All Danes born before 1994 and diagnosed with ASD from 1959 to 2013 (n = 2,277) were identified from the Danish medical registries. We used Cox proportional hazards regression to compare the risk of receiving permanent social security benefits in the ASD patients compared with an age- and gender-matched general population cohort. Using the DREAM database, we calculated work participation score and proportion of patients working or not working at the age of 30 years. Median follow-up from ASD diagnosis was 23.4 years (range 0.2 to 59.3). ASD patients had a higher risk of receiving permanent social security benefits (hazard ratio 2.3 [95% confidence interval 2.1 to 2.6]) compared with the comparison cohort with 24% of the ASD patients receiving permanent social security benefits at the end of follow-up compared with 12% of the comparison cohort. At the age of 30 years, the proportion not working was 28% in the ASD cohort and 18% in the comparison cohort. In patients with ASD, 23% of those without a job had a psychiatric diagnosis. In conclusion, the risk of receiving permanent social security benefits was twice as high in patients with ASD and the work participation score was reduced compared with the background population.