Congenital heart disease (CHD) is associated with risk factors of central nervous system (CNS) infections including infective endocarditis, cardiac shunt physiology, and immune deficiencies. We aimed to investigate the risk of CNS infections in the CHD population compared to the general population. In this cohort study, we used Danish nationwide medical registries to identify individuals diagnosed with CHD at any age, born between 1977 and 2012. For each CHD individual, we matched 10 individuals on sex and birth year from the general population. Subjects were followed until first-time hospital diagnosis of CNS infection, death, emigration, or end of study. We computed cumulative incidences of CNS infections with death as a competing risk, as well as hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) adjusted for birth year and sex. We identified 17,550 individuals with CHD (50% male). Among subjects with CHD, the cumulative incidence of CNS infection at age 30 years was 1.0% compared to 0.6% in the general population. The overall HR of CNS infections in CHD subjects relative to the general population was 2.1 (95% CI 1.6–2.7). The HR was 1.9 (95% CI 1.4–2.7) for mild to moderate CHD, 2.1 (95% CI 1.3–3.3) for severe CHD and 3.0 (95% CI 1.1–8.2) for univentricular physiology. The HR for CHD subjects without record of infective endocarditis was 2.0 (95% CI 1.5–2.5). The risk of CNS infections was increased among individuals with CHD compared to the general population, and the risk was not limited to individuals with infective endocarditis.