Objective. To investigate the efficacy of minimally invasive transcatheter closure of congenital heart disease (CHD) under the guidance of transesophageal ultrasound. Methods. A total of 100 patients with CHD treated in our hospital from February 2019 to April 2020 were enrolled in the group. The patients were randomly divided into control group and research group. The control group received minimally invasive transcatheter closure under the guidance of X-ray, and the research group received minimally invasive transcatheter closure under the guidance of transesophageal ultrasound. The operative results, the intraoperative- and postoperative-related indexes, and the incidence of early postoperative complications and follow-up results were compared. Results. First of all, we compared the results of the two groups: 48 cases of success, 2 cases of difficulty in the research group, 35 cases of success, 11 cases of difficulty, and 4 cases of failure in the control group. The success rate in the research group was higher than that in the control group (
P
<
0.05
). Secondly, we compare the relevant indicators in the process of operation. The operation time, cardiopulmonary bypass time, upper and lower cavity obstruction time, and blood transfusion volume in the research group were lower than those in the control group (
P
<
0.05
). In terms of postoperative-related indexes, the ventilator-assisted time, 24 h postoperative drainage, ICU time, and postoperative hospital stay in the research group were all lower than those in the control group (
P
<
0.05
). The incidence of early postoperative complications in the research group was significantly lower than that in the control group such as secondary pleural hemostasis, pulmonary infection, pleural effusion, subcutaneous emphysema, poor incision healing, phrenic nerve loss, and right lower limb numbness (
P
<
0.05
). All patients were followed up for 6 months, and the cardiac function of both groups returned to normal. There was no significant difference in the incidence of postoperative residual shunt and new tricuspid regurgitation. There was no significant difference in the data (
P
>
0.05
). Considering abnormal ECG events, the incidence of abnormal ECG events (complete right bundle branch block, incomplete right bundle branch block, second- and third-degree block, left anterior branch block) in the research group was significantly lower than that in the control group (
P
<
0.05
). Conclusion. Minimally invasive transcatheter closure of CHD under the guidance of transesophageal ultrasound has the advantages of less trauma, less blood loss, short hospital stay, simple operation, less postoperative complications, and remarkable therapeutic effect. Minimally invasive transcatheter closure under the guidance of transesophageal ultrasound has the advantage of adapting to a wide range of syndromes and can be used for the closure of CHD in children. According to different types of CHD, registering the corresponding occlusive pathway can improve the success rate of operation. Through postoperative reexamination and regular follow-up, it is proved that minimally invasive transcatheter closure under the guidance of transesophageal ultrasound is safe, effective, and feasible.