Atrial septal defect is a common congenital heart disease, producing a left-to-right shunt in the atrial septum; the current preferred treatment is transcatheter device closure. The aim is to conduct a systematic review to synthesize information on the comparative effectiveness and safety of atrial septal defect closure devices. The methods used: a comprehensive search of Ovid MEDLINE®, Embase, and Cochrane Central databases was conducted. Studies comparing procedural and follow-up outcomes of atrial septal defect devices were included. Network meta-analyses were conducted to generate direct and indirect evidence for comparative effectiveness and safety outcomes between devices. The results are as follows: Twelve studies met our inclusion criteria and were compared in network meta-analyses. The meta-analyses evaluated contemporary devices: the AMPLATZER Septal Occluder; the GORE CARDIOFORM Septal Occluder; the Figulla Flexible II Occluder; the CeraFlex Septal Occluder; and the HELEX Septal Occluder. These studies represented 3998 patients. The primary safety and efficacy outcomes were device embolization and follow-up residual shunt, respectively. Secondary clinical outcomes included procedural success and major and minor complications. No differences were found between devices in terms of device embolization and secondary clinical outcomes. Follow-up residual shunt was higher with the HELEX Septal Occluder compared with the AMPLATZER Septal Occluder (odds ratio 2.92, 95% confidence interval 1.12–7.61). To conclude: although most outcomes were similar between devices, evidence was largely based on observational low-quality studies. There were inconsistencies in outcome reporting and definitions; this merits future studies, with head-to-head device comparisons and standardization of outcomes.