The use of neurohormonal blockade (NHB) therapy is associated with increased survival and improved quality of life in patients with left ventricular assist devices (LVADs). The INTERMACS study was a retrospective cohort analysis that included 12,144 patients with continuous-flow LVADs, 85.8% of whom were treated with NHB, which included single, double or triple therapy using angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, β-blockers or mineralocorticoid-receptor antagonists. Patients receiving any NHB therapy had a significant increase in survival compared with those not receiving NHB therapy. Furthermore, patients receiving triple therapy had the lowest risk of death in unadjusted and adjusted models. These findings suggest that the optimal treatment regimen for heart failure after LVAD implantation is similar to guideline-directed therapy for heart failure with reduced ejection fraction.