Background: The percutaneous closure of single atrial septal defect (ASD) is a valid alternative to surgery. Objectives: To assess the feasibility of percutaneous treatment of multiple ASDs. Methods: Between 1998 and 2007, 165 out of 1280 consecutive patients undergoing ASD percutaneous closure at our institution showed multiple defects that were classified in four categories: double atrial septal defects (d‐ASD), multifenestrated atrial septal defects (f‐ASD), multifenestrated defects with no signs of right heart overload (f‐PFO), and complex cases (c‐ASD). The following end points were taken into consideration: (1) immediate procedural success; (2) long term safety and efficacy. In this study, up to 81% of multiple ASDs were suitable for percutaneous closure. Results: Multiple device implantations were required in 47% of cases, especially in patients with d‐ASD and c‐ASD. Complication rate, residual shunt, and long term outcome were comparable among the four different categories. In particular, at long term follow‐up (6 ± 2 years) no patient required further surgical or percutaneous treatment and complete closure was confirmed in 99% of cases. Conclusions: Percutaneous closure of multiple ASDs is feasible and associated with a good outcome. A thorough identification and analysis of morphological aspects are mandatory in order to select the appropriate device and the optimal strategy. © 2010 Wiley‐Liss, Inc.