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To achieve sinus rhythm, ablation of long-standing persistent atrial fibrillation (LSPAF) usually requires substrate modification in addition to pulmonary vein isolation (PVI). In the present article, we aimed to compare clinical and substrate modification effects of 2 distinct PVI strategies during stepwise ablation in patients with LSPAF: (1) Combined approach: cryoballoon (CB) for PVI and radiofrequency (RF) ablation for substrate modification and (2) RF-only approach: RF ablation for both PVI and substrate modification.A total of 34 patients were divided into 2 groups: 19 in the combined group and 15 in the RF group. Left atrial (LA) complex fractionated atrial electrogram (CFAE) maps were acquired before and after PVI and compared between groups. The groups were compared for acute atrial fibrillation termination (AFT) rates and long-term arrhythmia-free survival.A significant reduction on total LA CFAE area was observed with PVI in both groups. In the CB group, when pulmonary veins were excluded, the reduction of LA CFAE area was the most significant on the posterior wall of left atrium and which was greater than in the RF group. Although the ratio of AFT was higher in the CB group (44% versus 33%, respectively), single-procedure arrhythmia-free survival at 1 year was comparable between groups (68% in the CB group versus 66% in the RF group). Times of total procedure, fluoroscopy and post-PVI RF were all shorter in the CB group.CB may cause greater substrate modification on the posterior wall and increase AFT rate during LSPAF ablation.