Background/ Aims: So far, surgical and interventional therapies for muscular ventricular septal defects ( mVSDs) beyond the moderator band have had their limitations. Thus, alternative therapeutic strategies should be developed. We present a new animal model for the evaluation of such strategies. Methods: In a pig model ( n = 9), anterolateral thoracotomy was performed for exposure of the left ventricle. mVSDs were created under two- and three- dimensional echocardiography with a 7.5- mm sharp punch instrument, which was forwarded via a left ventricular puncture without extracorporeal circulation. Results: Creation of mVSDs was successful in all animals ( n = 9) confirmed by echocardiography, hemodynamic measurements and autopsy. The defects were located in the midmuscular ( n = 4), apical ( n = 1), inlet ( n = 2) and anterior part ( n = 2) of the muscular septum. All animals were hemodynamically stable for further procedures. The diameter and shunt volume of the mVSDs were 4.8 - 7.3 mm ( mean: 5.9 mm) and 12.9 - 41.3% ( mean: 22.1%), respectively. Autopsy confirmed in all animals the creation of a substantial defect. Conclusion: The described new technique for creation of an mVSD on the beating heart in a pig model is suitable for the evaluation of new therapeutic strategies for mVSD closure. Copyright (C) 2008 S. Karger AG, Basel.