OBJECTIVE:: We sought to summarize the preliminary clinical experience of minimally invasive transthoracic device closure of perimembranous ventricular septal defects with a new delivery system without cardiopulmonary bypass. METHODS:: Twenty-one patients aged 11 months to 12 years (median age, 3.6 years) with isolated perimembranous ventricular septal defects underwent minimally invasive device closure with an inferior sternotomy of 3 to 5 cm under transesophageal echocardiographic guidance. A single per–right ventricular U-like suture was established, and a new delivery system was introduced, aided by a 16-gauge trocar, including a guidewire, proper sheath, and loading sheath. The proper size of devices was determined by means of transesophageal echocardiographic analysis, and then the device was released under real-time transesophageal echocardiographic monitoring if no significant aortic regurgitation, abnormal atrioventricular valvular motion, or residual interventricular shunt appeared. RESULTS:: All of the defects were successfully closed. No residual shunt, noticeable aortic or tricuspid regurgitation, or significant arrhythmias appeared during more than 5 months of follow-up. CONCLUSION:: Minimally invasive transthoracic device closure of perimembranous ventricular septal defects with a new delivery system without cardiopulmonary bypass is feasible and safe under transesophageal echocardiographic guidance. However, it is necessary to evaluate the intermediate and long-term results.