Stereotactic arrhythmia radioablation (STAR) was introduced to treat ventricular tachycardia (VT) refractory to catheter ablation. No data are now available in the septal VT substrate setting, representing a challenge when using conventional techniques. This study sought to evaluate the arrhythmic burden in patients with septal VT treated with magnetic resonance-guided STAR (MRgSTAR). We enrolled consecutive patients with septal VT substrate. The therapy target was achieved by combining anatomic/functional and electrophysiologic information. Patients were treated with a single fraction of 25Gy adopting MRgSTAR. All patients were clinically followed up, and all implantable cardiac devices were remotely monitored. The efficacy outcome included recurrences of any sustained VT beyond the 6-week blanking period after MRgSTAR. The safety outcome was the incidence of adverse events and atrioventricular block. We included 11 patients with septal substrate VT (median age: 68 years; Q1-Q3: 64.5-78 years; 100% male). Clinical presentation was an electrical storm in 81.8% of patients. No complications occurred after MRgSTAR, and 6(54.5%) patients were discharged on the same day of treatment. During a mean follow-up of 12 ± 6months, the efficacy outcome occurred in 3 (27.3%) cases. A significative reduction of implantable cardioverter-defibrillator (ICD) therapy (23.6 before MRgSTAR vs 1.7 after MRgSTAR; P< 0.001) was observed. Left ventricular ejection fraction increased significantly after treatment (38% [Q1-Q3: 33.5%-42.0%] before MRgSTAR vs 43.8% [Q1-Q3: 35%-47%] after MRgSTAR; P=0.04). No adverse effects were observed in the implantable cardioverter-defibrillator and lead system; in the 7 patients with preserved atrioventricular conduction, no atrioventricular block was reported. MRgSTAR represents a safe and effective strategy for treating septal VT.