Abstract Background Congenital heart disease (CHD) is the most common major birth defect. Due to improvements in early detection and treatment during the last decades, most children survive into adulthood and currently the proportion of adults with CHD surpasses that of children. Previous studies reported an increased comorbidity prevalence in patients with simple CHD compared to a population without CHD. However, it is unclear whether these comorbidities increase the risk of death more in patients with simple CHD compared to those without. Purpose To investigate whether 40-years old individuals with simple CHD are at 1) an increased risk of developing stroke and acute myocardial infarction (AMI) and 2) whether AMI and stroke survivors with simple CHD have increased 10-year mortality compared to non-CHD matched controls. Methods Patients with simple CHD aged 40 years between 1977–2008 were identified by linking the Danish nationwide registries. Simple CHD was defined as isolated ventricular septal defect, atrial septal defect, patent ductus arteriosus or pulmonary stenosis. Patients with simple CHD were matched with 100 birthdate- and sex matched controls who did not have any CHD. We used two multiple Cox regression to compare the risk of AMI and stroke, respectively, between patients with and without simple CHD. Reported were the standardized 10-year risks for fixed comorbidity distribution according to simple CHD status. In patients who developed AMI or stroke, we used two other multiple Cox regressions to compare the risk of death between patients with and without simple CHD. Reported were the standardized 10-year risks for fixed comorbidity distribution according to simple CHD status in patients with AMI and stroke, respectively. Results We identified 2307 patients with simple CHD (54% females). The risk of developing AMI or stroke among 40-years old individuals with simple CHD was comparable to the risk in the background population – a trend of higher risk among simple CHD was seen but was not significant. The 10-year mortality after developing AMI was higher among the population with simple CHD than the matched controls (Figure 1) e.g. 10-year mortality: CHD 26.9% vs controls 20.6%. This was also the case for the 10-year mortality after developing a stroke (Figure 2) e.g. 10-year mortality 24.8% vs controls 22.6%. Conclusions Middle-aged individuals with simple CHD are not at an increased risk of developing AMI or stroke compared to the background population. However, developing stroke or AMI among individuals with simple CHD is associated with increased mortality compared to individuals without simple CHD. In the aging CHD population, the risk of atherosclerotic disease is naturally increasing. Therefore, it is of the utmost important to study long-term complications further to guide both primary and secondary prevention of cardiovascular disease in these vulnerable individuals. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Danish Heart Foundation