As adult patients with congenital heart disease (CHD) grow older, the risk of developing coronary artery disease (CAD) increases. We sought to estimate the prevalence of CAD in adult patients with CHD, the safety of coronary angiography in this setting, and the potential relation of CAD to clinical and hemodynamic parameters. Two hundred fifty adult patients with CHD (mean age 51 +/- 15 years; 53% men) underwent selective coronary angiography in our center for reasons other than suspected CAD. Clinical and hemodynamic data were retrieved retrospectively from medical records and echocardiographic and angiographic databases, respectively. Significant CAD using quantitative coronary angiography was found in 9.2% of adult patients with CHD. No patient with cyanosis or age <40 years had significant CAD. Systolic and diastolic systemic ventricular dimensions were significantly higher in patients with CAD, even after adjustment for age (odds ratio [OR] for 10-mm increase 2.59, 95% confidence interval [CI] 1.29 to 5.21, p = 0.007; OR 2.31, 95% CI 1.24 to 4.31, p = 0.008, respectively). Systemic arterial hypertension and hyperlipidemia were strong predictors of CAD (OR 4.54, 95% CI 1.82 to 12.0, p = 0.001; OR 9.08, 95% CI 3.56 to 24.54, p <0.0001, respectively), whereas no relation to chest pain was found. Only 1 major adverse event was recorded during coronary angiography. In conclusion, the prevalence of significant CAD in a hospital adult CHD cohort was similar to that in the general population. This study supported the performance of selective coronary angiography in patients >40 years referred for cardiac surgery, with low risk of major complications. Traditional cardiovascular risk factors for CAD also applied to adult patients with CHD, in whom primary prevention of CAD was as important as in the general population.