Background: Radiofrequency catheter ablation (RFCA) has been shown to have low efficacy for the treatment of persistent atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM). We conducted this study to evaluate the benefit of adjunctive vein of Marshall (VOM) ethanol infusion during RFCA for persistent AF (PsAF) in patients with non-obstructive HCM. Methods: This multicenter retrospective observational study included 102 consecutive non-obstructive HCM patients with PsAF who underwent RFCA plus VOM ethanol infusion (VOM-EI) (RFCA + VOM, n = 56) or RFCA alone (RFCA, n = 46) for the first time. The efficacy endpoint was survival without AF or atrial tachycardia (AT) after the blanking period. Results: We completed the VOM-EI in 92.9% (52/56) patients. The left pulmonary vein antrum ablation time (RFCA + VOM: 19.9 \pm 6.1 min vs. RFCA: 27.2 \pm 9.3 min), mitral isthmus (MI) ablation time (RFCA + VOM: 16.9 \pm 3.7 min vs. RFCA: 28.4 \pm 7.8 min), and rate of coronary sinus (CS) vein ablation (RFCA + VOM: 57.69% vs. RFCA: 80.43%) were lower but the acute success rate of MI block (RFCA + VOM: 98.1% vs. RFCA: 84.8%) were higher in the RFCA + VOM group than those in the RFCA group (all p 0.05). After twelve months follow-up, 84.6% of patients (44/52) survived without AF/AT in the RFCA + VOM group, compared to 65.2% of patients (30/46) in the RFCA group (p = 0.03; odds ratio = 2.93, 95% CI: 1.18–7.79). Conclusions: VOM-EI combined with RFCA decreased the recurrence rate of AF/AT at 12 months in HCM patients with PsAF. VOM-EI simplified the ablation of the left pulmonary vein antrum and MI and increased the success rate of MI bidirectional block.