Adults with congenital heart disease (CHD) are an increasing population requiring cardiac operations. To date, the perioperative risk factors for this group have not been identified. This study aimed to identify clinical, morphologic, and hemodynamic risk factors for an adverse outcome. This study retrospectively analyzed a cohort of 500 patients (ages >16 years) who underwent 543 operations between January 2004 and December 2008 at a single center. The composite end point of an adverse outcome was in-hospital death, a prolonged intensive care exceeding 4 days, or both. The composite end point was reached by 253 of the patients (50.6%). Of the 500 patients, 13 (2.6%) died within 30 days after the operation. After logistic regression analysis, the following eight items remained significant: male gender (P = 0.003; odds ratio [OR] 1.8; 95% confidence interval [CI] 1.2–2.6), cyanosis (P > 0.006; OR 3.7; 95% CI 1.5–9.4), functional class exceeding 2 (P = 0.004; OR 2.2; 95% CI 1.3–3.7), chromosomal abnormalities (P = 0.004; OR 3.3; 95% CI 1.4–7.7), impaired renal function (P = 0.019; OR 3.8; 95% CI 1.2–11.5), systemic right ventricle (RV) in a biventricular circulation (P = 0.027; OR 3.3; 95% CI 1.1–9.5), enlargement of the systemic ventricle (P = 0.011; OR 1.7; 95% CI 1.1–2.6), and operation with extracorporeal circulation (P = 0.002; OR 4.3; 95% CI 1.7–11.4). Early mortality in the current adult CHD population is low. Morbidity, however, is significant and influenced by the patients’ conditions (male gender, chromosomal abnormalities), history (cyanosis, New York Hospital Association [NYHA] class), and underlying morphology (systemic RV). This information for a large cohort of patients could help progress toward more adequate counseling for adults with a congenital heart defect.