Introduction: In patients with non-paroxysmal AF, various ablation strategies have been attempted to target non-pulmonary vein (PV) foci or to achieve substrate modification beyond pulmonary vein isolation (PVI). The efficacy of empirical ablation of the SVC, one of the most common non-PV foci, is unclear. The aim of this study was to investigate the efficacy and safety of additional superior vena cava (SVC) isolation in patients with non-paroxysmal atrial fibrillation (AF) undergoing thoracoscopic surgical ablation. Methods and Results: A total of 191 patients with persistent or longstanding persistent AF was enrolled. All patients underwent total thoracoscopic surgical ablation for AF, and half of them also received empirical SVC isolation. We compared the atrial-tachyarrhythmia (ATa)-free survival rate and procedure-related complications in the two groups of patients. The 3-year ATa-free survival rate was 53% in the SVC-isolation group and 52% in the no-SVC-isolation group, (p = 0.644). There were no differences between the two groups with respect to AF type or LA size. Procedure-related complications occurred in 12 patients (6%). Pacemakers were implanted only in 3 patients from the SVC-isolation group. The only factor influencing recurrence of ATa was LA diameter. Conclusions: Empirical SVC isolation during thoracoscopic ablation for persistent AF did not improve patient outcomes.