Abstract Background Catheter ablation (CA) with pulmonary vein isolation (PVI) is an optimal treatment option in patients with paroxysmal atrial fibrillation (AF). PVI alone in patients with persistent AF has proved to have suboptimal results. Ablation of additional atrial structures, such as posterior wall (PW) and left atrial appendage has been investigated as a tool to improve procedural efficacy. Recently very high-power short-duration (vHPSD) ablation was developed to allow rapid PVI, limiting complication through the maximization of resistive heating, and minimization of conductive heating. Objectives Compare PVI plus PWI using vHPSD versus standard-power (SP) ablation index-guided CA among consecutive patients with persistent AF Methods Forty consecutive patients underwent PVI plus PW isolation using vHPSD, compared to 40 controls underwent standard power (SP) PVI plus PW isolation. The primary efficacy endpoint outcome was recurrence of atrial tachyarrhythmias after a 3-month blanking period. The primary safety outcome was a composite of major complications within 30 days of CA. Results Treated patients have a median age of 62.8±9 years, 68 (85%) are male. Median left atrial volume is 42.4 (36-50) ml/m2. 61 (78.8%) patients had never undergone catheter ablation before. There are no statistically significant differences between groups. PW isolation was obtained more commonly in the vHPSD compared to the SP group (98% vs. 75%, p=0.007), despite shorter procedure and fluoroscopy times (p<0.001). Survival free from recurrent atrial tachyarrhythmias at 18 months was 68% in the vHPSD and 47% in SP groups, respectively (log-rank p=0.071), without major adverse events. The vHPSD approach was significantly associated with reduced risk of recurrent AF at multivariable analysis (HR, 0.39, p=0.030). Conclusions The results show feasibility and safety of posterior wall vHPSD ablation for persistent AF using this new temperature-controlled catheter without intraprocedural and periprocedural major complications at follow-up. vHPSD ablation for PW isolation may be more effective in term of atrial tachyarrhythmias recurrences with a trend for superior efficacy. However, this remains a single center experience in a small group of patients. Comparative trials involving greater number of patients with long-term follow-up are necessary to definitive results.