Background: Previous meta-analyses comparing efficacy and safety of uninterrupted novel oral anticoagulants (NOACs) versus uninterrupted vitamin K antagonist (VKA) during catheter ablation (CA) of atrial fibrillation (AF) had no consensus in major bleeding, and didn’t perform subgroup analyses for different types of major bleeding events. This meta-analysis was performed to comprehensively evaluate the risk of major bleeding events of these two anticoagulant strategies during CA of AF.Methods: We searched online databases for randomized controlled trials that compared major bleeding events of uninterrupted NOACs and VKA during CA of AF up to January 2021. A fixed-effect model was used if the chi-squared test P-value was > 0.10 and I2 was < 50%, otherwise a random- effect model was used.Results: Six published studies including 2392 patients were identified for inclusion in the analysis. The overall incidence of major bleeding events was lower in the NOACs group than in the VKA group (OR = 0.56, 95% CI = 0.34 – 0.93, I2 = 38%, P = 0.15). Subgroup analyses showed that the incidence of severe puncture site complications was lower in the NOACs group than in the VKA group (OR = 0.53, 95% CI = 0.30 – 0.96, I2 = 16%, P = 0.32). But the incidence of cardiac tamponade (OR = 0.53, 95% CI = 0.23 – 1.26, I2 = 0%, P = 0.46), intracranial (OR = 0.25, 95% CI = 0.03 – 2.23, I2 = 0%, P = 0.82) and gastrointestinal bleeding (OR = 0.98, 95% CI = 0.18 – 5.39, I2 = 0%, P = 0.43) had no statistically significant differences between the two groups.Conclusion: This meta-analysis suggests that compared to uninterrupted VKA, uninterrupted NOACs are superior in major bleeding and severe puncture site complications during CA of AF, but are not superior in cardiac tamponade, intracranial and gastrointestinal bleeding.