BACKGROUND: Iron overload cardiomyopathy is a significant cause of morbidity and mortality in transfusion-dependent thalassemia patients. Standard iron chelation therapy is less efficient in alleviating iron accumulation in many organs, especially when iron enters the cells AIM: To validate our hypothesis that adding amlodipine to the iron chelation regimen is more efficient in alleviating myocardial iron overload. METHODS: Five databases, including PubMed, Cochrane Library, Embase, ScienceDirect, and ClinicalTrials.gov, were systematically searched, and three randomized controlled trials involving 144 pediatric patients with transfusion-dependent thalassemia were included in our meta-analysis based on the predefined eligibility criteria. The quality of the included studies was assessed based on the Cochrane collaboration tool for bias assessment. The primary outcome assessed was myocardial-T2 and myocardial iron concentration, while the secondary results showed serum ferritin level, liver iron concentration, and treatment adverse outcomes. Weighted mean difference and odds ratio were calculated to measure the changes in the estimated treatment effects. RESULTS: During the follow-up period, Amlodipine treatment significantly improved cardiac T2 by 2.79 ms compared to the control group [95% confidence interval (CI): 0.34-5.24, CONCLUSION: Amlodipine with iron chelation therapy significantly improved cardiac parameters, including cardiac-T2 and myocardial iron, in patients with transfusion-dependent thalassemia without causing significant adverse events but enhancing the efficacy of iron chelation therapy.