Abstract Background In patients undergoing repeat catheter ablation for atrial fibrillation (AF) two ablation strategies beyond pulmonary vein isolation (PVI) have recently gained increased interest: posterior wall isolation (PWI) using pulsed field ablation (PFA) and Vein of Marshall (VoM) ethanol ablation combined with radiofrequency energy ablation (RFA). However, a direct comparison is lacking. Purpose To compare prospectively enrolled patients undergoing repeat catheter ablation for persistent AF using PVI and PWI with PFA (PFA group) vs. PVI and VoM ethanol ablation using RFA (VoM group) regarding procedural characteristics, safety, myocardial injury and outcomes. Methods Patients undergoing redo PFA-PVI with PWI and VoM ethanol ablation with RFA were included. Isolation and bidirectional block were checked using a multipolar mapping catheter. High-sensitivity cardiac troponin T (hs-cTnT) was measured after 24h of ablation. Results A total of 84 patients were included (age 69 [interquartile range (IQR) 63-75] years; ejection fraction 56% [IQR 48-60%]; left atrial size 42 [IQR 37-47] mm), baseline characteristics did not differ significantly between groups. Of these, 54 patients (64%) were in the PFA group and 30 (36%) in the VoM group. The procedure duration (65 [IQR 56-73] minutes vs 116 [IQR 103-142] minutes; p < .001) and fluoroscopic times (11 [IQR 8–14] minutes vs 14 [IQR 12-19] minutes; p < .001) were significantly shorter for the PFA group than for the VoM group. No major complications were observed except for a probable allergic reaction in the VoM group and a transient AV-block in the PFA group. High-sensitivity cardiac troponin levels post ablation were similar between the PFA group and the VoM group with 886 [IQR 627–1260] ng/L and 793 [IQR 543-1199] ng/L, p=0.28, respectively. During follow-up (median duration 230 [IQR 117-370] days), AF recurrence was observed in 15% in the PFA group and in 40% in the VOM group (p ≤ 0.01). Conclusion In patients undergoing repeat catheter ablation for AF, PVI and PWI using PFA is associated with shorter procedure and fluoroscopic times, similar high-sensitivity cardiac troponin levels and a reduced recurrence rate compared to PVI using RFA with additional VoM ethanol ablation.Central Illustration