Objective     To introduce the application of transcatheter closure of multi-fenestrated atrial septal defect (ASD) via femoral vein under ultrasound guidance with amplatzer cribriform occluder (ACO) and atrial septal defect occluder (ASDO), as well as to assess its feasibility, effectiveness and safety. Methods     The clinical data of 48 patients with fenestrated ASD occluded via femoral vein under ultrasound guidance from December 2015 to May 2018 in our hospital were retrospectively analyzed, including 17 males and 31 females, aged 10 months to 51 years, an average of 11.50±13.86 years, and weighting 6-79 (27.00±20.14) kg. Among 48 patients with fenestrated ASD, 12 patients had double-foramen and 13 atrial septal aneurysm combined with defects and 23 multi-foramen. All patients underwent transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE) to complete the closure of fenestrated ASD. Ultrasound, electrocardiogram and chest X-ray were reviewed the next day after surgery to evaluate the curative effect. Results     Forty-eight patients with ASD were treated with 49 occluders, due to one patient with two occluders. There were 29 ASDO (8-26 mm) and 20 ACO (18-34 mm). During the operation, TTE/TEE examination showed that 48 patients were completely occluded, 13 patients showed fine bundle shunt in the unreleased push notification rod, and 9 patients had fine bundle shunt after the release of push notification rod. Fine bundle shunt was found in 8 patients 24 hours after operation, and microshunt was found in 3 patients 1 year after operation. All the patients were followed up. The occluder position was good. The right heart was reduced in different degrees, and the X-ray showed that the pulmonary blood was reduced in different degrees. No arrhythmia was found by electrocardiogram after operation. Conclusion     It is a safe and effective method to use ACO and ASDO to occlude ASD through femoral approach under ultrasound guidance.