Abstract Background Ablation of drivers in persistent atrial fibrillation (AF) has shown controversial results. Purpose To test the efficacy of a tailored approach for persistent AF ablation which includes pulmonary vein isolation (PVI) plus “subjective” identification and ablation of drivers. Methods From May 2017 to December 2019, selected patients with persistent AF and ongoing AF at the beginning of the ablation procedure were included. Conventional high-density mapping catheters (PentaRay NAV, IntellaMap Orion or Advisor HD Grid) were used. Drivers were subjectively identified as: a) fractionated continuous (or quasi-continuous) electrograms on 1–2 adjacent bipoles, without dedicated software (Figure 1A, dashed line; PR = PentaRay NAV); and b) sites with spatiotemporal dispersion (i.e. all the cycle length comprised within the mapping catheter) plus non-continuous fractionation on single bipoles (Figure 1B, arrows; in panels A and B: paper speed 200 mm/s; ORB = 24-pole ORBITER Woven catheter, blue bipoles around tricuspid annulus and green bipoles into the coronary sinus). Ablation included PVI + focal or linear ablation targeting sites with drivers. Ablation success was defined as conversion to sinus rhythm or atrial flutter during ablation. Follow-up included visits with 24h Holter ECG at 3–6–12 months. Survival free from atrial arrhythmias lasting >30 seconds was compared between patients ablated with this tailored approach, and all consecutive patients with persistent AF treated with a PVI-only strategy during the same period. Results 158 Patients received ablation: 35 with the tailored approach (61,7±10,2 years; 29% females) and 123 with only PVI (62,5±9,6 years; 25% females; 89% cryoablation). Basal characteristics were similar (Table 1). In the tailored-approach group, 14 patients (40%) presented 28 detectable sites with continuous fractionated electrograms, 26 on the left atrium and 2 on the right atrium, which was only mapped if ablation of drivers in the left atrium was not successful; 12 (43%) were located within the pulmonary vein antra. 27 patients (77%) showed 103 sites with spatiotemporal dispersion (4 [3–5] per patient). Ablation success was achieved in 17 patients (48%; conversion to sinus rhythm, n=7; conversion to atrial flutter, n=10) in the tailored-approach group and 1 patient (0,8%, sinus rhythm) in the PVI-only group. Excluding a 3-month blanking period, the tailored approach, compared to only PVI, improved one-year freedom from atrial arrhythmias (71% Vs 51%, p=0,05) and mean survival free from atrial arrhythmias (26±3 months; 95% CI 21–32 months Vs 18±2 months; 95% CI 15–22 months) (Figure 1C), at the cost of a longer median procedural time (246 [212–277] vs 108 [81–143] min, p<0,001) and fluoroscopy time (51 [36–76] vs 33 [21–45] min, p<0,001). Conclusion Subjective identification and ablation of drivers, added to PVI, improved freedom from atrial arrhythmias. Funding Acknowledgement Type of funding sources: None. Table 1. Basal characteristicsFigure 1