The presence of a large ventricular septal defect (VSD) may affect the surgical treatment of congenital heart defects. VSD size and shape by two-dimensional echocardiography (2DE) and at autopsy were compared in 18 patients, average age 6 months, who had 2DE studies shortly prior to death. Six had isolated VSD and the other 12 had additional cardiac anomalies. The maximal diameter of the VSD was measured in long- and short-axis views and the VSD area was calculated assuming an elliptical shape. A large VSD was present in 11 of 18 (61%) and was correctly detected by 2DE in 10 of 11 (91%, no false positives). 2DE-predicted area of VSDs correlated with autopsy measurements (r = 0.94). The shape and orientation of the VSD were correctly predicted by 2DE (16 of 18); it was elliptical in 13 and circular in five, with the major axis of the elliptical VSDs aligned with the short axis of the heart in eight and with the long axis in five. The diameters of the VSD ranged from 3 to 25 mm (r = 0.93). Diameters measured from the long-axis and short-axis views correlated with autopsy (r = 0.98 and 0.89, respectively). Thus: (1) 2DE was useful in distinguishing large VSDs from smaller defects, and in measuring their diameters and areas. (2) The shape and orientation of the VSD were well predicted by 2DE.