The purpose of this study was to assess the value of echocardiography for intraoperative guidance during closure of perimembranous ventricular septal defects (pmVSD) and to assess outcomes of these patients. We identified and assessed 78 patients who underwent 2- and 3-dimensional echocardiography-guided mini-invasive per-atrial closure of pmVSD in the cardiac surgery department of our institution, from February 2016 to August 2018, and 76 patients who underwent transcatheter closure of VSD guided by fluoroscopy at the pediatric department (percutaneous control group). All the patients underwent echocardiography. Their clinical data were retrospectively reviewed and analyzed. All patients were followed up using transthoracic echocardiography (TTE) for a maximum of 24 months after the closure. All patients underwent successful device implantation. Echocardiography showed that the major immediate complications included residual shunt, pericardial effusion, and tricuspid regurgitation in the per-atrial group. During the mid-term follow-up period, TTE revealed that the most common complication was tricuspid regurgitation (non-preexisting). There were no cases of VSD recurrence, device displacement, valvular injury, malignant arrhythmias, hemolysis, or death. Moreover, according to the TTE data, the intracardiac structure of the patients were improved. Compared to the control group, the intracardiac manipulation time was shorter and the number of patients with residual shunts, redeployment of devices, or immediate new tricuspid regurgitations was fewer when using 2- and 3-dimensional echocardiography. However, the procedure time in the per-atrial group was slightly longer than that in the control group. Two- and 3-dimensional echocardiography are feasible monitoring tools during mini-invasive per-atrial VSD closure. The short- and mid-term follow-up showed satisfactory results compared to fluoroscopy.