• In the distressed newborn, the presence or absence of congenital heart disease (CHD) may be difficult to determine on clinical grounds alone. We prospectively studied 104 infants who were younger than 7 days of age and in whom CHD was suspected. The presence of CHD was detected noninvasively in 64 infants. The other 40 infants were considered not to have CHD. None of these 40 infants underwent cardiac catheterization for the purpose of excluding CHD, although three (7.5%) were subsequently found to have incidental cardiac lesions. In nine (14%) of the patients with CHD, the noninvasive diagnosis was incomplete. In four patients, ventricular septal defects were not detected; in another patient, a suspected ventricular septal defect was not confirmed at catheterization. In addition, three abnormalities of the great vessels were misdiagnosed noninvasively. We conclude that cardiac catheterization is not necessary to exclude significant CHD in the distressed newborn resulting from noncardiac causes, but significant diagnostic errors regarding anomalies of the aortic arch and ventricular septal defects may occur, based on the noninvasive evaluation alone.