The purpose of this study was to evaluate the safety and efficacy of transcatheter Atrial septal defect (ASD) closure guided by transthoracic echocardiography (TTE). Since 2004, ASD closure was performed successfully in total 337 patients. Transthoracic echocardiography guidance was used in 206 patients (61.1%) (group 1). Closure was guided by transesophageal echocardiography under general anesthesia in patients with poor transthoracic acoustic windows, defects with aneurysmatic septum and/or multiple defects in 131 patients (38.9%) (group 2). The median age (9 vs. 16 years, P < 0.001), mean defect diameter (14.9 ± 4 vs. 17.2 ± 5 mm, P < 0.001), ratio of complex atrial septal defect (14 vs. 34%, P = 0.01), the median balloon stretch dimensions (21 vs. 18.7 mm, P = 0.003) and the median device diameters (22 vs. 19 mm, P < 0.001) were significantly greater in group 2 compared to group 1. Both the median procedure time and the median fluoroscopy time was significantly shorter in group 1 (60 vs. 75; and 13 vs. 16.5 min; P < 0.0001 and P < 0.0001, respectively). The incidence of residual shunt did not differ significantly in two groups during follow up. Transthoracic echocardiography guidance during transcatheter ASD closure is safe and effective in children and in many adults. Even complex ASDs could be closed with TTE in patients with good acoustic windows. Performing the procedure under TTE guidance significantly reduces procedure time and also provides increased patient’s comfort.