In this report, we present 12 patients (range 14–76 years, mean 40 ± 22.7 years) who underwent surgical repair of a ventricular septal defect (VSD). Location, size, and surrounding anatomy of the VSD were assessed prior to intervention in all patients with live/real time three-dimensional transthoracic echocardiography (3DTTE). In 9 patients, measurements of maximum dimension, circumference, and area by 3DTTE correlated well with the same measurements from intraoperative three-dimensional transesophageal echocardiographic (3DTEE) reconstruction. 3DTTE measurement of maximum dimension of VSDs also agreed well with maximum dimension by surgery in 10 patients. Live/real time 3DTTE accurately defined VSD location, size, and surrounding anatomy in all patients studied by us. VSD characterization by live 3DTTE agreed well with surgery descriptions and 3DTEE measurements.