Our previous study showed that combined therapy with deferiprone (L1) and deferoxamine (DFO) was safe and efficacious in reducing iron overload in poorly-chelated thalassemia major patients for the short-term but the magnetic resonance imaging (MRI) T2* evaluation was not available at that time. Since October 2006, we applied a standardized chelation protocol by stratifying transfusion-dependent thalassemic patients into three groups, namely well-chelated group (A), poorly-chelated group without (B) or with (C) risk of cardiac complications, based on their serum ferritin (SF) levels and magnetic resonance imaging (MRI) cardiac T2* measurements. The patients in each group were given options of chelation regimens to improve their iron overload status. Chelation regimens included continuation or intensification of DFO alone (Regimen Ic or Ii, respectively), L1 alone (Regimen II), and combined therapy with L1 and DFO (Regimen III). Group A patients continued with Regimen Ic. Group B patients could opt for either Regimen Ii or II/III. Group C patients could opt for either Regimen Ii or III. Serum ferritin levels and MRI cardiac and liver T2* measurements were evaluated after 1 year of treatment. Fifty-seven patients (27 males, 30 females; age range 5-34 years, median: 25 years) were categorized into Group A (n = 3), B (n = 20) and C (n = 34). All Group A patients continued with DFO treatment. In Group B, seven were on Regimen Ii, five on Regimen II and five on Regimen III. In Group C, five were on Regimen Ii, two on Regimen II and 26 on Regimen III. Significant improvement was noted only for Group C patients using Regimen III (combined therapy) in SF levels, cardiac T2* and liver T2* measurements.