Abstract Background Left atrial fibrosis is related to atrial fibrillation (AF) recurrence after AF ablation. However, the benefit of patient-specific substrate modification guided by fibrosis delineated on voltage mapping or magnetic resonance imaging (MRI) is conflicting. Objective To compare the efficacy and safety of additional modification of left atrial fibrosis [identified by low-voltage area (LVA) or late gadolinium-enhancement on MRI] vs. circumferential pulmonary vein isolation (PVI) with or without stepwise ablation not targeting fibrosis in AF. Methods A systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials was performed from inception to November 2022. Only randomized studies investigating the utility of fibrosis-guided substrate modification beyond conventional PVI were included. The primary outcome was a recurrence of any atrial arrhythmia. Major adverse events and procedural, fluoroscopic, and total ablation time were defined as secondary outcomes. We calculated pooled estimates of the outcomes by a random-effect model and reported them as risk ratio (RRs) and 95% confidence interval (CI). Results A total of 9 studies (8 randomized controlled clinical trials and 1 randomized design within a prospective study) and 2135 patients with AF were included. The atrial arrhythmia recurrence was lower in the additional fibrosis-guided ablation group (RR 0.82; 95% CI 0.71-0.94; p=0.006) (Figure 1A). No differences were found between fibrosis-guided substrate modification and conventional PVI group in major adverse events [RR 1.25 (0.55-2.81), p=0.598)] and mean differences of procedural time [-2.88 (-40.34 to 34.57) min], fluoroscopic time [1.82 (-1.86 to 5.49) min], and total ablation time [-14.28 (-48.70 to 20.14) min]. In the stratified analyses, there were no interactions of the lower atrial arrhythmia recurrences within the modality of fibrosis identification (LVA vs. delayed enhancement on MRI), type of AF (paroxysmal vs. persistent), the burden of LVA (no or low vs. high), and strategy of the control group (PVI only vs. PVI plus stepwise ablation) (Figure 1B). Conclusion By incorporating two modalities of left atrial substrate evaluation – voltage mapping and MRI – we conclude that the individually tailored fibrosis-guided ablation in AF is associated with a lower recurrence after catheter ablation.