Catheter ablation for persistent atrial fibrillation (PeAF) is particularly challenging, as the clinical outcomes are modest. Pulmonary vein isolation (PVI) plus linear ablation is one of the main strategies for PeAF ablation. Completely durable transmural lesions are difficult to achieve by catheter ablation during mitral isthmus ablation. The ligament of Marshall contains the vein of Marshall (VOM), myocardial tracts and innervation, and serves as arrhythmogenic foci that make it an attractive target in catheter ablation of atrial fibrillation. Additionally, it co-localizes with the mitral isthmus, and may serve as a part of the perimitral isthmus reentrant circuit. Ethanol infusion into the VOM results in rapid ablation of the neighboring myocardium and its innervation. Its incorporation into PVI significantly increases the success rate of mitral isthmus block and the clinical outcome of PeAF ablation.