Objectives: The ablation index (AI)-guided high-power ablation for pulmonary vein isolation (PVI) apears 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 AI-guided high-power ablation strategy among patients with AF after PVI. Methods: Data from 53 patients with AF were collected. Mapping and ablation of SVC was 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 radiofrenquency (RF) was recorded. The RF applications and AI value in different SVC walls were compared and analyzed. Results: 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 SVCI procedure was 9.5±4.5 min. RF applications at anteroseptal wall was 38 (10.8%) points in 20 (43.5%) patients, posteroseptal wall was 74 (21.0%) points in 38 (82.6%) patients, posteral wall was 81 (22.9%%) points in 40 (87.0%%) patients, anteroseptal wall was 72 (20.4%) points in 37 (80.4%%) patients, anterolateral wall was 45 (12.7%) points in 27 (58.7%) patients, anteroseptal wall was 43 (12.2%) points in 23 (50.0%) patients. The mean AI value in septal, posterior and anterior walls was higher than that of lateral wall. There was no complication in any cases. Conclusion: AI-guided high-power ablation is feasible and safe strategy in performing SVCI. The RF applications and AI value in different SVC walls varied.