Objective: To determine whether TTE can provide safety and efficacy equivalent to TEE for assessment and guidance of transcatheter ASD occlusion using the Amplatzer septal occluder (ASO) in pediatric patients. Background: Most centers currently employ TEE for definitive ASD assessment and guidance of transcatheter ASD occlusion with the ASO. Methods: A prospective randomized trial of ASD closure using the ASO from March 2008 to April 2012. Key inclusion criteria were: isolated secundum ASD, age 2-18 years, and adequate TTE windows. Forty patients were enrolled and randomized to either TEE or TTE. In the TEE group, we used conventional ''stop flow'' balloon sizing. In the TTE group, we used the average ASD diameter from three standard views times 1.2 to determine device size. Baseline and follow-up (1-2 days, 1 month, and 6-12 months) ECGs, TTEs, and examinations were obtained for all patients. Results: Patient general and hemodynamic characteristics were similar in both groups. Procedural success was 100% in both groups. The average TEE stop flow diameter was similar to the scaled TTE diameter (15.35 6 4.62 vs. 16.57 6 5.47 mm; P = 0.46). Device size (16.0 6 4.94 vs. 16.37 6 5.05 mm, P = 0.82) and ratio of device to defect size (1.0 6 0.06 vs. 0.99 6 0.03, P = 0.52) were also similar. Total fluoroscopy (13.6 6 6.17 vs. 8.9 6 8.45 min, P = 0.007), procedure (70.6 6 22.98 vs. 51.1 6 17.61 min, P = 0.005), and room (126.8 6 28.41 vs. 95.7 6 20.53 min, P = 0.0004) times were all significantly shorter in the TTE group. Neither group had significant procedural complications or in follow-up. Rates of shunt resolution were also similar. Conclusions: This study suggests that the use of TTE is as efficacious and safe as TEE for assessment and guidance of ASD occlusion using the ASO. Reduced fluoroscopy time appears to be a safety advantage of TTE. TTE may also reduce costs because of lower requirements for laboratory time and ancillary staff.