AIMS: Voltage-based ablation is a promising catheter ablation strategy for atrial fibrillation (AF) in which low-voltage zones (LVZs) are targeted as a complement to pulmonary vein isolation (PVI). In a randomized setting, we intend to investigate whether PVI plus ablation of LVZs, compared to PVI-only, decreases the incidence of arrhythmia recurrence and improves health-related quality of life (HRQoL) in patients with persistent AF and LVZs. METHODS AND RESULTS: Individually designed ablation of low-voltage areas in persistent atrial fibrillation trial (IDEAL-AF; NCT04377594) is a multi-centre, randomized, controlled clinical trial. Patients with persistent AF and LVZs ≥ 3.0 cm² outside the PVI ablation lines will be randomized in a 1:1 ratio to either PVI or PVI plus LVZ ablation. The primary outcome will be the recurrence of atrial arrhythmias off anti-arrhythmic drugs during 12 months of follow-up after one to two ablation procedures within 6 months. A 3-month blanking period will be applied after the first procedure. Patients will be monitored using a smart phone-based ECG recording device throughout the follow-up period. With an anticipated enrolment of 936 patients, this study has 80% power to detect a 20% absolute risk reduction in the primary endpoint. Additionally, HRQoL improvement will be assessed using three questionnaires. CONCLUSION: IDEAL-AF is a multi-centre, randomized, controlled clinical trial investigating whether ablation of LVZs in addition to PVI reduces the recurrence rate of atrial arrhythmias and improves HRQoL compared to PVI-only in patients with persistent AF and LVZs. This study has the potential to modify recommendations regarding ablation techniques for this specific patient cohort.