The amount of fibrosis in the left atrium (LA) predicts atrial fibrillation (AF) recurrence after catheter ablation (CA). We aim to identify whether regional variations in LA fibrosis affect AF recurrence.This post-hoc analysis of the DECAAF II trial includes 734 patients with persistent AF undergoing first-time CA who underwent Late Gadolinium Enhancement Magnetic Imaging Resonance (LGE-MRI) within one month prior to ablation and were randomized to MRI-guided fibrosis ablation in addition to standard pulmonary vein isolation (PVI), or standard PVI only. The LA wall was divided into seven regions: anterior, posterior, septal, lateral, right pulmonary vein (PV) antrum, left PV antrum, and left atrial appendage (LAA) ostium. Regional fibrosis percentage was defined as a region's fibrosis prior to ablation divided by total LA fibrosis. Regional surface area percentage was defined as an area's surface area divided by the total LA wall surface area before ablation. Patients were followed up for a year with single-lead ECG devices.The left PV had the highest regional fibrosis percentage (29.30 ± 14.04%), followed by the lateral wall (23.23 ± 13.56%), and the posterior wall (19.80 ± 10.85%). The regional fibrosis percentage of the LAA was a significant predictor of AF recurrence post-ablation (OR = 1.017, p = 0.021), and this finding was only preserved in patients receiving MRI-guided fibrosis ablation. Regional surface area percentages did not significantly affect the primary outcome.We have confirmed that atrial cardiomyopathy and remodeling is not a homogenous process, with variations in different regions of the LA. Atrial fibrosis does not uniformly affect the LA, and the left PV antral region has more fibrosis than the rest of the wall. Furthermore, we identified regional fibrosis of the LAA as a significant predictor of AF recurrence post-ablation in patients receiving MRI-guided fibrosis ablation in addition to standard PVI.