Background: Lesions of adjacent structures have been reported after closure of large atrial septal defects with the Amplatzer septal occluder. In children, growth of the heart should modify the initial relationship between the device and surrounding structures. Aim: To compare the relationship between large Amplatzer septal occluder and adjacent cardiac structures at short-, mid-, and long-term follow-up in at-risk paediatric population using echocardiography. Methods: A total of 25 children (4.6±2.9 years old, 18 girls) with the largest atrial septal defect devices implanted between 1997 and 2002 were enrolled prospectively for complete echocardiogram 17.8±10.5 months (mid-term follow-up) and 8.8±0.9 years (long-term follow-up) after the procedure. Results were compared with the echocardiogram carried out 2.1±3.4 days after the procedure (short-term follow-up). Results: The minimal distance between the left disk and the mitral valve increased: 1.4±2.0 mm at short-term and 5.1±2.3 mm at long-term follow-up (p<0.05), leading to less contact between the disk and the anterior leaflet and less mitral regurgitation (10 at short-term, 4 at long-term follow-up, p<0.05). The number of devices straddling the aorta decreased from 17 to 12 at long-term follow-up (p<0.05). There was protrusion of disk in the venous structure in seven patients on the first echocardiogram, which disappeared at long-term follow-up. Conclusion: Although frequently in close contact with the aortic root, mitral valve, or venous returns, large devices tend to centre and move away from the surrounding structures, with decreased risk for long-term distortion.