The effectiveness of deferoxamine (DFO), deferiprone (DFP), or deferasirox (DFX) in thalassemia major was assessed. Outcomes were reported as means±SD, mean differences with 95% CI, or standardized meandifferences. Statistical heterogeneity was tested using χ2(Q) and I2. Sources of bias and Grading of Recommendations Assessment, Development and Evaluation system (GRADE) were considered. Overall, 1520 patients were included. Only 7.4% of trials were free of bias. Overall measurements suggest low trial quality(GRADE).The meta-analysis suggests lower final liver iron concentrations during associated versus monotherapytreatment (p<0.0001), increases in serum ferritin levels during DFX 5, 10, and 20 mg/kg versus DFO-treatedgroups (p<0.00001, p<0.00001, and p=0.002, respectively), but no statistically significant difference duringDFX 30 mg/kg versus DFO(p=0.70), no statistically significant variations in heart T2* signal during associated orsequential versus mono-therapy treatment (p=0.46 and p=0.14, respectively), increases in urinary ironexcretion during associated or sequential versus monotherapy treatment (p=0.008 and p=0.02, respectively),and improved ejection fraction during associated or sequential versus monotherapy treatment (p=0.01 andp<0.00001, respectively). These findings do not support any specific chelation treatment. The literature showsrisks of bias, and additional larger and longer trials are needed.