Achieving acute and durable mitral isthmus (MI) block remains challenging using radio frequency (RF)-catheter ablation alone. Vein of Marshall (VoM) ethanolisation results in chemical damage along the mitral isthmus resulting in the creation of a durable transmural lesion with a very high rate of procedural block. However, no studies have systematically assessed the efficacy of MI ablation alone when no anatomical VoM is present. Thirty seven patients without VoM evidenced after careful angiographic examination were included. Ablation parameters and result were compared to a matched control group in whom the posterior MI line was performed without assessing the presence of the VoM. MI block was achieved in 36 out of 37 patients without VoM (97%), with endocardial ablation only in 5/37 (14%) and combined endocardial and CS ablation in 32/37 patients (86%). There was a significant difference in occurrence of block between patients without a VoM and the control group (97,3% vs. 65% respectively, p<0,01), with a trend towards less needed RF (26 (IQR 20-38) vs 29 (IQR 19-40) tags (p=0.8), 611 (IQR 443-805) vs 746 (IQR 484-1193) seconds (p=0.08)). The absence of a Vein of Marshall is associated with a very high rate of procedural block during posterior mitral isthmus ablation. The higher rate of MI block in this specific population would also suggest the crucial role of the Vein of Marshall (when present) in resistant MI block.