Iron deficiency with or without anemia is a common comorbidity co-existing with heart failure patients and is an independent risk factor for heart failure exacerbation and worse prognosis. A growing number of randomized clinical trials and meta-analysis evaluated the clinical efficacy and safety of intravenous iron use in heart failure patients. However, the findings from them are inconsistent and often conflicting. This meta-analysis was performed based on PRISMA (Preferred Reporting Items or Systematic Reviews and Meta-Analyses) guidelines after registering in PROSPERO (CRD42023395888). A literature search was conducted using a systematic search of PubMed, Embase, and Scopus databases until September 30, 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4. Out of 4585 studies evaluated, 16 randomized control trials with 6739 acute or chronic heart failure patients were included for analysis. The intravenous iron therapy significantly lowered the composite HF hospitalization or cardiovascular death (OR 0.56; 95% CI 0.40 to 0.79; I2 = 83%, P = 0.001), HF hospitalization (OR 0.69, 95% CI 0.54 to 0.90; I2=57%, P=0.005), improved 6-minute walk test (MD: 20.02 (95% CI 8.16 to 31.87; I2=40%, P=0.0009), and the change in mean LVEF (MD: 2.03, 95% CI 0.49-3.58; P=0.010). The risks of total and serious adverse events were not significantly increased with the Iron therapy compared to the placebo/standard of care group. Based on this meta-analysis, the intravenous iron intervention among heart failure patients with iron deficiency significantly reduced the risk of hospitalization from heart failure exacerbation. In addition, there was improved exercise performance and left ventricular function from baseline with no significant increased risk of serious adverse events.