Objective To verify whether hybrid surgical and interventional ablation(HA) for the treatment of persistent atrial fibrillation (AF) is superior to video-assisted thoracoscopic surgical radiofrequency ablation (VATS-RA). Methods From September 2010 to December 2017, 79 consecutive patients with persistent AF underwent VATS-RA or HA in Fuwai Hospital. VATS-RA was performed in sixty patients (a stand-alone surgical group, 48 males and 12 females, at average age of 56.0±7.6 years, and HA was performed in nineteen patients (a hybrid group, 14 males and 5 females, at average age of 58.0±7.3 years). Follow-up was completed at 3 months, 6 months, 1 year and annually thereafter. Postoperative sinus rhythm was defined as sinus rhythm recorded in 24-hour or 7-day Holter during follow-up, without exhibited rapid atrial tachyarrhythmia≥30 s including AF, atrial flutter, or atrial tachycardia. Results Seventy-eight patients (98.7%) completed the follow-up. Although the preoperative left atrial diameter (49.1±5.3 mm) in the hybrid group was significantly greater than that in the stand-alone surgical group (41.7±6.2 mm, P<0.001). Overall sinus rhythm maintenance rate in the hybrid group was significantly greater than that in the stand-alone surgical group (94.7% versus 64.4%,P=0.011). And sinus rhythm maintenance rate free from anti-arrhythmic drugs (AADs) and catheter ablation in the hybrid group was significantly greater than that in the stand-alone surgical group (84.2% versus 50.8%, P=0.010). Conclusion HA is superior to VATS-RA in the treatment of persistent AF, but a larger sample size is needed for further validation in prospective randomized studies.