BackgroundRandomized clinical trials (RCTs) evaluating the role of intravenous (IV) iron administration in patients with heart failure (HF) and iron deficiency (ID) have yielded inconsistent results.MethodsElectronic search of MEDLINE, EMBASE and OVID databases was performed until November 2022 for RCTs that evaluated the role of IV iron administration in patients with HF and ID. The main study outcomes were the composite of HF hospitalization or cardiovascular mortality, and individual outcome of HF hospitalization. Summary estimates were evaluated using random effects model.ResultsThe final analysis included 12 RCTs with 3,492 patients (1,831 patients in the IV iron group and 1,661 patients in the control group). The mean follow-up was 8.3 months. IV iron was associated with a lower incidence in the composite of HF hospitalization or cardiovascular mortality (31.9% vs. 45.3%; relative risk [RR] 0.72; 95% confidence interval [CI] 0.59–0.88) and individual outcome of HF hospitalization (28.4% vs. 42.2; RR 0.69; 95% CI 0.57–0.85). There was no significant difference between both groups in cardiovascular mortality (RR 0.88; 95% CI 0.75–1.04) and all-cause mortality (RR 0.95; 95% CI 0.83–1.09). IV iron was associated with lower New York Heart Association class and higher left ventricular ejection fraction (LVEF). Meta-regression analyses showed no effect modification for the main outcomes based on age, hemoglobin level, ferritin level or LVEF.ConclusionAmong patients with HF and ID, IV iron administration was associated with reduction in the composite of HF hospitalization or cardiovascular mortality and driven by a reduction in HF hospitalization.