Introduction: The purpose of this study was to investigate the clinical value of real-time three-dimensional transesophageal echocardiography (RT-3D-TEE) for percutaneous transcatheter closure of multiple secundum atrial septal defects (ASDs) using a Chinese domestic occluder device. Methods: From July 2008 to September 2011, 37 patients (mean age 28.4 +/- 9.7 years; 24 females) with multiple secundum ASDs underwent percutaneous transcatheter closure in our institution with custom-made occluder devices. RT-30-TEE was used to clarify the diagnosis and to help determine the operation scheme before the procedure, for real-time monitoring and guiding the operation during the procedure, and for evaluating the result shortly after the procedure. Results: The custom-made atrial septal occluders were successfully implanted in 36 patients under RT-3D-TEE guidance. Twenty-seven patients were implanted with two devices and 9 patients with a single device. In two patients where the distance between the two defects was less than 7 mm (5.5 mm and 6 mm), double occluder devices were also successfully implanted. One patient underwent surgery for the complication of unstable occluder and increased residual shunt after closure. No other severe complications were observed. Conclusions: RT-3D-TEE provides reliable diagnostic evidence of multiple ASDs and can help the clinician to select an appropriate operation scheme according to the number and morphology of multiple defects prior to percutaneous transcatheter closure. It also allows for proper positioning of the devices during the procedure and provides an effective means of evaluating the success of the procedure. For two devices to be implanted simultaneously in multiple ASDs, the usual requirement for the distance between the two defects may differ between our domestically made devices and the Amplatzer occluder.