The purpose of this study was to determine the possibility of a new surgical technique for the treatment of ventricular septal rupture after acute myocardial infarction. The operations were conducted under the guidance of real-time three-dimensional echocardiography (RT3DE) (iE33, Philips Medical Systems, Andover, MA). Six pigs were anesthetized, and after median sternotomy, the echo probe was applied directly to the surface of the heart. A ventricular septal defect (VSD) was created in all the six porcine hearts. The VSDs were closed with an Amplatzer septal occluder (AGA Medical Corp, Golden Valley, MN) through the right ventricular free wall under RT3DE monitoring. The procedure was successful in all the six pigs. The VSDs were precisely closed with the septal occluder under RT3DE guidance. Both left ventriculography and color-Doppler echocardiography showed no residual shunt in any of the six pigs. The use of the Amplatzer septal occluder under the guidance of real-time three-dimensional echocardiography made it possible to close the ventricular septal defect safely and successfully without the need to resort to cardiopulmonary bypass. Our results strongly suggest that the application of this new technique is feasible for the treatment of ventricular septal rupture after acute myocardial infarction.