Background: Studies have demonstrated that catheter ablation of atrial fibrillation is associated with better rhythm control than drug therapy. The present study aimed to assess the clinical outcomes and health-related quality of life of ablation therapy in a real world setting. Methods: A prospective, non-randomized, single center study in a real-world clinical setting in China was conducted. Patients were followed up at 3, 6, and 9 months after baseline encounter. Propensity score matched patients receiving ablation or anti-arrhythmic drug therapy were compared. Incidence rate of atrial fibrillation recurrence and quality of life outcomes were measured and analyzed using log-rank test, multivariate logistic regression and mixed-effects linear regression respectively. Results: In this study, 151 atrial fibrillation patients treated by ablation therapy and 318 patients treated by antiarrhythmic drugs were enrolled. During follow up, 82.0% in the ablation arm and 22.4% in the drug arm had no documented atrial fibrillation recurrence [HR for atrial fibrillation recurrence 0.07 (95% CI: 0.02-0.21, p < 0.0001)] among paroxysmal atrial fibrillation patients. The corresponding no recurrent rate were 66.7% and 18.5% [0.21 (0.05-0.95, p = 0.04)] respectively among persistent atrial fibrillation patients. Improvement in Short Form-36 physical component scores, Short Form-36 mental component scores and total Atrial Fibrillation Effect on Quality-of-life scores were 16.33 (14.05-18.61, p < 0.001), 8.10 (6.11-10.09, p < 0.001) and 18.28 (16.11-20.45, p < 0.001) respectively among paroxysmal AF patients and 6.32 (3.15-9.49, p < 0.001), 3.99 (1.82-6.16, p < 0.001) and 13.97 (10.89-17.05, p < 0.001) respectively among persistent AF patients. Improvements in total Atrial Fibrillation Effect on Quality-of-life score were also significant in ablation arm while no significant improvement of total Atrial Fibrillation Effect on Quality-of-life score in the drug arm. Conclusion: Compared with drug therapy, catheter ablation is associated with significant lower AF recurrence and improved overall quality of life.