BACKGROUND: Trials studying iron repletion in patients with chronic heart failure (CHF) and iron deficiency are underpowered to find consistent hard endpoint (mortality and hospitalization) reductions. We conducted a meta-analysis of controlled trials to examine the effects of iron repletion on these parameters. METHODS AND RESULTS: Pubmed, CENTRAL, EMBASE and NIH Clinical Trials databases were searched for controlled trials utilizing intravenous iron, with or without erythropoietin, in patients with CHF with NYHA class ≥ II, iron deficiency, and left ventricular dysfunction. Data regarding hospitalizations, mortality, adverse events, NYHA class, and ejection fraction were extracted, analyzed for heterogeneity, and pooled using the DerSimonian and Laird random effects model. We identified 5 controlled trials (n = 631 patients). Patients treated with intravenous iron had significant reductions in hospitalizations (OR 0.26, 95% CI 0.08-0.80), adverse events (OR 0.35, 95% CI 0.21-0.60), NYHA class (mean improvement 1.2 classes, 95% CI 0.69-1.78, and LVEF (mean improvement 5.0%, 95% CI 0.13-9.80) but no relationship was found on mortality (OR 0.66, 95% CI 0.30-1.44). CONCLUSION: Treatment of iron deficiency in patients with CHF reduces the risk of hospitalizations without increased adverse events, suggesting its role as a potential therapeutic target in this group of patients.