Objectives: This study sought to assess the effects of neurohormonal therapies in preventing cardiotoxicity in patients receiving chemotherapy. Background: Various cardioprotective approaches have been evaluated to prevent chemotherapy-related cardiotoxicity; however, their overall utility remains uncertain. Methods: This meta-analysis included randomized clinical trials of adult patients that underwent chemotherapy and neurohormonal therapies (β-blockers, mineralocorticoid receptor antagonists, or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) versus placebo with follow-up ≥4 weeks. The primary outcome was change in left ventricular ejection fraction (LVEF) from baseline to the end of the trial. Other outcomes of interest were measures of LV size, strain, and diastolic function. Pooled estimates for each outcome were reported as standardized mean difference and weighted mean difference between the neurohormonal therapy and placebo groups using random effects models. Results: We included 17 trials, collectively enrolling 1,984 participants. In pooled analysis, neurohormonal therapy (vs. placebo) was associated with significantly higher LVEF on follow-up (standardized mean difference: +1.04 [95% confidence interval (CI): 0.57 to 1.50]) but with significant heterogeneity in the pooled estimate (I2 = 96%). Compared with placebo-treated patients, those randomized to neurohormonal therapies experienced a 3.96% (95% CI: 2.90 to 5.02) less decline in LVEF estimated by weighted mean difference, but with significant heterogeneity (I2 = 98%). There was a trend toward lower adverse clinical events with neurohormonal therapy (vs. placebo) that did not meet statistical significance (risk ratio: 0.80 [95% CI: 0.53 to 1.20]; I2 = 71%). Conclusions: Neurohormonal therapies are associated with higher LVEF in follow-up among cancer patients receiving chemotherapy, although absolute changes in LVEF are small and may be within inter-test variability. Furthermore, significant heterogeneity is observed in the treatment effects across studies highlighting the need for larger trials of cardioprotective strategies.