Low-voltage areas (LVAs) in the left atrium may promote atrial fibrillation (AF), but the efficacy of LVA ablation for preventing arrhythmia has not been determined. In the present study, we carried out a multicenter, randomized controlled trial (SUPPRESS-AF) to investigate the efficacy of LVA ablation in patients with persistent AF who had left atrial LVAs. Patients with persistent AF and left atrial LVAs that covered ≥5 cm of the left atrial surface on a voltage map after pulmonary vein isolation (PVI) were randomized to undergo LVA ablation (PVI + LVA-ABL group) or not (PVI-alone group) in a 1:1 fashion. Recurrence of AF or atrial tachycardia (AT) was monitored using 24-h Holter electrocardiography (ECG) and twice-daily portable ECG recordings. The primary endpoint was freedom from AF or AT recurrence without antiarrhythmic drug use during 1 year of follow-up. Of 1,347 patients (1,003 males and 344 females) who underwent initial ablation for AF, patients with left atrial LVAs were assigned to the PVI + LVA-ABL (n = 170) or the PVI-alone group (n = 171). Although the PVI + LVA-ABL group demonstrated a numerically higher rate of freedom from AF or AT recurrence compared with the PVI-alone group (61% (95% confidence interval (CI) = 53-68%) versus 50% (95% CI = 42-57%)), this difference did not reach statistical significance (P for log(rank) test = 0.127). There was no difference in the procedure-related serious adverse events between the two groups (1.7% versus 1.8%, P < 0.0001). In conclusion, LVA ablation in addition to PVI did not significantly reduce 1-year AF or AT recurrence in patients with persistent AF with left atrial LVAs. Future studies are needed to identify patients who may receive greater benefit from LVA ablation.