Although effective, transcatheter closure of perimembranous ventricular septal defects (pmVSD) with the Amplatzer Membranous VSD Occluder (AGA Medical Corporation, MN) carries a substantial risk of complete heart block, prompting many to abandon this intervention. A newly designed Amplatzer device for pmVSD was modified, in part, to minimize this risk. After rigorous preclinical testing, we report the first human experience with the Amplatzer Membranous VSD Occluder 2 (AGA Medical Corporation) in two patients (a 5-year old with a 12-mm pmVSD and a 26-year-old male with a 8-mm defect). Both procedures were successful, with no adverse events at 7 and 4 weeks of follow-up, respectively. Herein, we discuss characteristics of the new device, potential advantages compared to the prior version, and main technical aspects related to the procedure. © 2013 Wiley Periodicals, Inc.