The aim of the study was to compare transesophageal echocardiography (TEE) and fluoroscopy for percutaneous atrial septal defect (ASD) closure.This was a retrospective analysis of children who underwent percutaneous ASD closure. The procedure was guided by TEE without fluoroscopy in 130 patients (TEE group) and by fluoroscopy in 163 patients (fluoroscopy group). Baseline demographic/clinical characteristics were recorded. Patients were followed until hospital discharge. Outcomes were procedure duration, peri/postoperative complications, hospital stay, and costs.The TEE and fluoroscopy groups showed no significant differences in age (71.7 ± 40.7 vs 62.5 ± 38.8 months), male/female ratio (54/76 vs 66/97), weight (22.0 ± 12.0 vs 20.1 ± 9.0 kg), ASD diameter (9.9 ± 4.2 vs 9.3 ± 3.9 cm), distances to the superior vena cava (13.4 ± 4.6 vs 13.3 ± 4.2 cm), inferior vena cava (13.4 ± 4.3 vs 13.9 ± 4.1 cm) and atrial septal roof (12.1 ± 4.0 vs 12.3 ± 3.2 cm), or atrial septal size (38.2 ± 6.2 vs 39.4 ± 26.6 cm); distance to the mitral valve was greater in the TEE group (13.2 ± 4.4 vs 11.3 ± 3.9 cm; P < .001). The TEE and fluoroscopy groups showed no significant differences in occlusion device size (14.3 ± 4.6 vs 13.8 ± 4.0 cm) or sheath size (8.7 ± 1.8 vs 8.7 ± 0.9 cm), but procedure duration was shorter in the TEE group (21.5 ± 14.6 vs 28.6 ± 10.9 minutes; P < .001). Postoperative fever (>38°C) occurred less frequently in the TEE group than in the fluoroscopy group (0.8% vs 9.2%; P < .001); there were no significant differences for the other complications. No patient had postoperative residual shunt, occlusion device shedding/displacement, or pericardial effusion. The TEE group had longer hospital stay (3.2 ± 0.6 vs 2.9 ± 0.6 days; P < .001) and higher procedure cost (29,687 ± 4218 vs 28,530 ± 1668 CNY (China Yuan); P = .002) than the fluoroscopy group.TEE-guided percutaneous ASD closure can be used as an alternative to fluoroscopy-guided procedures and avoids the use of radiation or contrast agents.