This study aimed to compare the long-term clinical outcomes and costs between using either transesophageal echocardiography (TEE) or X-ray fluoroscopy for Percutaneous atrial septal defect (ASD) closure in children. An analysis was conducted on clinical data from children undergoing TEE-guided (n = 168) and X-ray-guided (n = 139) percutaneous ASD closure. Demographic characteristics, technical indices, acute complications, follow-up outcomes, and costs were compared between the groups. The results are that TEE-guided closure demonstrated shorter surgical times (20.3 ± 7.6min vs. 32.8 ± 7.9min, P < 0.001) and lower procedural costs ($3093.3 ± 451.5 vs. $3589.1 ± 219.4, P < 0.001) compared to X-ray guidance. Initial successful closure rates were similar between the groups (TEE: 98.2%, XR: 97.1%, P = 0.691). TEE guidance also resulted in fewer acute complications and reduced radiation exposure. TEE-guided percutaneous ASD closure offers advantages in terms of shorter surgical times, lower procedural costs, and reduced radiation exposure compared to X-ray guidance. These findings support the preference for TEE guidance in pediatric ASD closure procedures, with potential implications for improving patient outcomes and reducing healthcare costs.