Introduction: Catheter ablation of the arrhythmogenic substrate reduces the recurrence of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillator (ICD). However, the all-cause mortality benefit in this population is unclear. Hypothesis: Prophylactic ablation of the arrhythmogenic substrate decreases all-cause mortality and prevents the recurrence of VT/ventricular fibrillation (VF) in patients with ischemic cardiomyopathy. Methods: We searched the MEDLINE and EMBASE databases from inception through May 2021. We included randomized controlled trials that compared all-cause mortality and ventricular arrhythmia recurrence in patients with ischemic cardiomyopathy who underwent ICD implantation with and without prophylactic ablation. The data from each study was combined using a fixed effects model to calculate the hazard ratio and 95% confidence interval (CI). Results: Four randomized controlled trials during 2007-2020 involving 505 patients (249 patients with and 256 patients without prophylactic VT ablation) were included in our meta-analysis. Compared with control, prophylactic VT ablation did not decrease the all-cause mortality (pooled hazard ratio = 0.94, 95% CI 0.54-1.63, p = 0.818, I2 = 5.8%). However, prophylactic VT ablation significantly decreased appropriate ICD therapy (pooled hazard ratio = 0.58, 95% CI 0.41-0.82, p = 0.002, I 2 = 26.1%) and VT/VF recurrence (pooled hazard ratio = 0.70, 95% CI 0.52-0.93, p = 0.015, I 2 = 0.0%). Conclusions: Prophylactic VT ablation in patients with ischemic cardiomyopathy did not decrease all-cause mortality; however, it did lead to decreased appropriate ICD therapy and VT/VF recurrence.