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Objective: Most published studies have aimed to compare the effectiveness of different treatment strategies for atrial fibrillation (AF), while few articles have comprehensively compared the safety of therapeutic measures.The aim of the article was to assess the safety of different therapeutic measures (different ablation techniques, antiarrhythmic drugs and surgery) in patients with AF., Method: A comprehensive and systematic search was undertaken across various databases, namely PubMed, Embase, Cochrane Library, and Web of Science, with the aim of identifying pertinent randomized controlled trials (RCTs) that delve into the safety aspects of diverse atrial fibrillation treatment strategies. The search was conducted up until December 1st, 2023. R4.2.3 software gemtc package was used for data analysis, Review Manager 5.3 was used for quality assessment of included studies, and stata15.0 was used for publication bias.Safety is defined as the adverse outcomes that occur in different treatment strategies for atrial fibrillation, with specific adverse events as described below., Result: 22 RCTs (involving 5073 subjects) with interventions including cryoballoon ablation (CA), radiofrequency ablation (RF), laser balloon ablation (LB), pulmonary vein ablation catheter (PVAC), antiarrhythmic drugs (AADS), and surgery (SA) were included in this study. In this article, medication and surgery were combined into the same intervention (non-traditional treatment measure, UT). UT was not associated with pericardial effusion (OR:4.27e-10, 95%CI:4.91e-30-0.0663), infections (OR:0.248, 95%CI:0.0584-0.89), arrhythmias (OR:0.609,95%CI:0.393-0.936), pseudoaneurysms (OR:5.57e-10, 95%CI:1.16e-31-0.934) and pulmonary vein stenosis (OR:1.16e-09, 95%CI:6.56e-24-0.194). Complications of the procedure were mainly mechanical injuries. Among the various ablation strategies, radiofrequency ablation had a lower incidence of phrenic nerve palsy and pain (OR:4.01e-06, 95%CI:1.18e-17-0.710) than cryoballoon ablation, which was superior to radiofrequency ablation in terms of infection rates. Finally, there were no significant differences between the various ablation techniques in terms of other complication rates., Conclusion: Because the interventions in the UT group were predominantly AADS and antiarrhythmic drug therapy didn't have some of the common aggressive complications of ablation strategies, the UT group had a low rate of complications such as pericardial effusion, postprocedural arrhythmia, pseudoaneurysm, and pulmonary vein stenosis compared with various catheter ablation strategies. Additionally, we also discovered between the various ablation technology groups, there was no significant difference in the incidence of major adverse events., Systematic Review Registration: PROSPERO registry number:CRD42024566530., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)