Female gender is associated with an increased recurrence of atrial fibrillation (AF) after catheter ablation (CA). Although AF is more common in men, women constitute a significant proportion with persistent atrial fibrillation (PsAF).The purpose of this study was to determine whether multiple ablation procedures improves arrhythmia outcomes in females with PsAF compared to men.We performed a multicenter observational study to determine long-term arrhythmia outcomes in patients undergoing >1 CA for PsAF. CA involved pulmonary vein (PV) isolation with additional ablation including linear, posterior wall isolation, electrogram-guided, or a combination of these.A total of 281 patients had >1 ablation procedure for PsAF and were included in this analysis (mean age 58.7 ± 9.3 years; 86 [30.6%] female; left atrial [LA] area 27.0 ± 5.3 cm; PsAF duration 1.7 ± 1.7 years). At mean follow-up of 45.5 ± 31.8 months, freedom from recurrent AF was present in 148 patients(52.7%) after 2.2 ± 0.5 procedures. After multivariate analysis, female gender (hazard ratio [HR] 2.10; P <.001) and enduring PV isolation (HR 1.64; P = .01) were independently associated with AF recurrence. Enduring PV isolation was significantly higher in women than in men (33.7% vs 19.5%; P = .01).2Female gender was independently and strongly associated with arrhythmia recurrence in patients undergoing multiple procedures for PsAF. PV reconnection was less likely, and fewer reconnected PVs occurred in women. Further studies are required to better understand the mechanisms responsible for AF in females to assist in closing the gender gap in the success of CA.