BACKGROUND It is unclear whether isolation of the Left atrial. posterior wall (LAPW) offers additional. benefits over pulmonary vein antrum isolation (PVAI) alone in patients with persistent atrial. fibrillation (AF). OBJECTIVE We sought to determine the impact of PVAI and LAPW isolation (PVAI+LAPW) versus PVAI alone on the outcome of ablation of persistent AF. METHODS During the first procedure, PVAI was performed in 20 patients (group 1), whereas in 32 patients (group 2), PVAI was extended to the Left atrial. (LA) septum and coronary sinus (CS), and isolation of the LAPW was targeted (ePVAI+LAPW). Isolation of the superior vena cava was achieved in both groups. ALL patients, regardless of arrhythmia recurrence, underwent a second procedure 3 months after the first procedure. In patients with reconnection of pulmonary veins or LAPW, reisolation was performed, and a third procedure was performed 3 months Later to verify isolation. Patients entered follow-up only after PVAI (group 1) or PVAI+LAPW (group 2) isolation was proven. RESULTS At the 1-, 2-, and 3-year follow-up examinations, the rates of freedom from atrial tachyarrhythmia without use of an antiarrhythmic drug were 20%, 15%, and 10% in group 1 and 65%, 50%, and 40% in group 2, respectively (Log-rank P < .001). The median recurrence-free survival. time was 8.5 months (interquartile range 6.5-11.0) in group 1 and 28.0 months (interquartile range 8.5-32.0) in group 2. CONCLUSION Proven isolation of the LAPW provides additional. benefits over PVAI alone in the treatment of persistent AF and improves procedural. outcome at follow-up. However, the ablation strategy of ePVAI+LAPW is still associated with a significant high incidence of very Late recurrence of atrial tachyarrhythmia.