BACKGROUND Direct comparisons of combined (C-ABL) and non-combined (NC-ABL) endo-epicardial ventricular tachycardia (VT) ablation outcomes are scarce. We aimed to investigate the long-term clinical efficacy and safety of these 2 strategies in ischemic heart disease (IHD) and nonischemic cardiomyopathy (NICM) patients. METHODS Multicentric observational registry including 316 consecutive patients who underwent catheter ablation for drug-resistant VT between January 2008 and July 2019. Primary and secondary efficacy endpoints were defined as VT-free survival and all-cause death after ablation. Safety outcomes were defined by 30-days mortality and procedure-related complications. RESULTS Most of the patients were male (85%), with IHD (67%) and mean age of 63±13 years. During a mean follow-up of 3±2 years, 117 (37%) patients had VT recurrence and 73 (23%) died. Multivariate survival analysis identified electrical storm (ES) at presentation, IHD, left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) class III/IV, and C-ABL as independent predictors of VT recurrence. In 135 patients undergoing repeated procedures, only C-ABL and ES were independent predictors of relapse. The independent predictors of mortality were C-ABL, ES, LVEF, age and NYHA class III/IV. C-ABL survival benefit was only seen in patients with a previous ablation (P for interaction=0.04). Mortality at 30-days was similar between NC-ABL and C-ABL (4% vs. 2%, respectively, P=0.777), as was complication rate (10.3% vs. 15.1% respectively, P=0.336). CONCLUSION A combined endo-epicardial approach was associated with greater VT-free survival and lower all-cause death in IHD and NICM patients undergoing repeated VT catheter ablations. Both strategies seem equally safe.