Neurohumoral antagonists are the foundation of heart failure therapy in patients with reduced left ventricular ejection fraction. Cardiac resynchronization therapy (CRT) has also been associated with improved outcomes in these patients. We aimed to evaluate the use of neurohumoral antagonists in patients ≥75 years compared with <75 years of age receiving CRT. We searched electronic databases, up to December 20, 2016 for all studies reporting medication use in patients ≥75 years and <75 years of age who received CRT. We used random-effects meta-analysis models to summarize the studies. We retained 12 studies (1 randomized trial and 11 observational studies) enrolling 5,728 ≥75 years old and 9,549 patients of <75 years old. There were lower use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers in patients ≥75 years compared with patients <75 years (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.47 to 0.74, p < 0.0001). In addition, there were lower use of mineralocorticoid receptor antagonists in patients ≥75 years compared with patients <75 years (OR 0.48, 95% CI 0.40 to 0.57, p < 0.0001). The use of β blockers was nonsignificantly lower in patients ≥75 years compared with patients <75 years (OR 0.70, 95% CI 0.47 to 1.03, p = 0.07). In conclusion, neurohumoral antagonists appeared to be underused in patients ≥75 years compared with patients <75 years receiving CRT. Consideration should be given to increase neurohumoral antagonism in patients ≥75 years referred for CRT.