Introduction: The ablation index (AI)-guided high-power ablation for pulmonary vein isolation (PVI) appears to be a novel strategy in treating atrial fibrillation (AF). This study aimed to evaluate the feasibility and safety of superior vena cava isolation (SVCI) by using an AI-guided high-power ablation strategy among patients with AF after PVI. Methods and Results: Data from 53 patients with AF were collected. Mapping and ablation of SVC were performed after PVI. The ablation power was set to 45 W and the ablation procedure was guided by AI. The SVC was divided into six segments in a cranial view. Applications and locations of radiofrequency (RF) were recorded. The RF applications and AI values in different SVC walls were compared and analyzed. SVCI was performed in 46 patients and electrical SVCIs were successfully achieved in all patients with a mean of 7.6 ± 2.9 RF applications. The mean time of the SVCI procedure was 9.5±4.5 min. The RF applications were located on different walls (anteroseptal anterior wall, 20/46 sites [43.5%]; posteroseptal wall, 38/46 sites [82.6%]; posterior wall, 40/46 sites [87.0%]; anterior walls, 37/46 sites [80.4%]; anterolateral wall, 27/46 sites [58.7%]; posterolateral wall, 23/46 sites [50%]). The mean AI value in septal, posterior, and anterior walls was higher than that of the lateral wall (392±28 vs 371±37, P < 0.001). There was no complication in any cases. Conclusion: AI-guided high-power ablation is a feasible and safe strategy for performing SVCI. The RF applications and AI value in different SVC walls varied.