Abstract Background Mineralocorticoid receptor antagonists (MRAs) are a cornerstone of heart failure therapy and have been shown to reduce the incidence of sudden cardiac death. However, a direct comparison between spironolactone and eplerenone in patients who present ventricular tachycardia (VT) is lacking. Purpose This study aimed to compare the effect of spironolactone and eplerenone on VT recurrence in patients with ischemic heart disease (IHD) hospitalized for VT episodes. Methods Our data utilized a registry of 405 patients with IHD and HF, who were hospitalized for an episode of sustained VT and received MRA therapy. We performed propensity score matching based on age, hypertension, diabetes, history of acute myocardial infarction, left ventricular ejection fraction (LVEF) and presentation with incessant VT. The matched population included 200 patients, stratified into two equivalent groups. Cox regression analysis was performed to identify predictors of VT recurrence, with Kaplan-Meier curves facilitating time-to-event analyses. Results The median age was 69 years and the majority (91%) were male. One-third had an ICD, and 41 patients (20%) had CRT. The median LVEF was 30%, 23 patients (12%) presented with an electrical storm, while 18 (9%) had incessant VT. VT led to hemodynamic instability in 91 cases (46%). Ablation was performed in 47 patients (24%), while 1 required mechanical circulatory support. Ablation was performed in 47 patients (24%), while 1 required mechanical circulatory support. Patients were followed for at least a year and median follow-up time was 414 days. A total of 78 patients had VT recurrence and 117 patients died. Eplerenone use significantly reduced the risk of VT recurrence compared to spironolactone (HR: 0.59 [0.37-0.93], p=0.023). This effect was consistent in the multivariate model as well (p=0.007). Conclusions Eplerenone use may confer a greater protective effect against VT recurrence in patients with IHD and sustained VT. Further studies are required to confirm these preliminary findings.