Abstract Background Early rhythm control within 1-year after atrial fibrillation (AF) diagnosis is associated with a lower risk of major adverse cardiovascular event (MACE). Recently, AF catheter ablation (AFCA) using cryoballoon ablation as initial therapy has been demonstrated to be superior to drug therapy for the prevention of AF recurrence in patients with paroxysmal AF. However, there is still lack of evidence whether AFCA for the method of early rhythm control is superior to medical rhythm control therapy for the reduction of MACE risk. Purpose To evaluate the association between rhythm control treatment and the risk of MACE for early rhythm control in AF patients Methods Using a Korean nationwide claims database, patients with AF who received rhythm control therapy including antiarrhythmic agents (AAD), direct current cardioversion (DCC), and AF catheter ablation (AFCA, radiofrequency ablation or cryoballoon ablation) within 1-year after AF onset between 2011 and 2020 were included. According to rhythm control treatment, patients were categorized two groups as follow: (1) medical rhythm control group who prescribed AAD or underwent DCC, and (2) AFCA group who underwent radiofrequency or cryoballoon ablation. The primary outcome was MACE, the composite of ischemic stroke, admission for heart failure (HF), and myocardial infarction (MI). For the safety outcome, the composite of cardiac tamponade, syncope, sick sinus syndrome, atrioventricular block, pacemaker implantation, and sudden cardiac arrest was evaluated. Multivariable Cox regression analysis were performed. Results A total of 229,056 pateints were included (mean age 67.3±13.6 and 59.4% of men). Mean duration from new AF diagnosis to rhythm control treatment was 29.1±69.2 days. Among total, 221,952 patients received medical rhythm control and 7104 patients received AFCA. Compared to medical rhythm control group, AFCA group was associated with lower risks of ischemic stroke, admission for HF, and MI (adjusted hazard ratio [95% confidence interval]: 0.342 [0.287-0.408], p<0.001 for ischemic stroke, 0.356 [0.282-0.451], p<0.001 for admission for HF, and 0.640 [0.452-0.906], p=0.011 for MI) (Figure A). AFCA for early rhythm control showed a significantly lower risk of MACE than medical early rhythm control (0.328 [0.283-0.380], p<0.001, Figure A). Compared to medical rhythm control, AFCA showed a similar risk for safety outcome (1.197 [0.920-1.556], p=0.180). Among AFCA group, cryoballoon ablation showed comparable risks of ischemic stroke (0.465 [0.113-1.922], p=0.290), admission for HF (0.262 [0.035-1.936], p=0.189), MI (0.823 [0.100-6.767], p=0.856), and MACE (0.449 [0.164-1.228], p=0.118) with radiofrequency ablation (Figure B). Conclusion Regarding on the method of early rhythm control for AF, catheter ablation of AF might reduce the risk of MACE without a significant increase of safety outcome to medical rhythm control. Further results from randomized clinical trials are needed.