Objective: Compare efficacy of Once a Month Single Dose Intravenous (Deferoxamine) with Daily Oral (Deferasirox) Iron Chelator in Thalassemia Major. Methodology: In this open label trials Patients were randomized by chit method after informed consent and allocated to two groups. Group A was administered Inj Deferoxamine by intravenous route once during monthly blood transfusions and Group B received Tab Deferasirox administered daily. The monitoring was done by serum Ferritin level every two months. Results: The primary outcome was decrease in ferritin level over 6 months from the baseline. Decrease in serum ferritin (%) over six months for Group A was 46±18 and Group B was 25±17 with significant difference between the two groups (p=0.001). The cost of treatment per kilo weight was not significantly different. Conclusion: We observed that Intravenous Deferoxamine once a month is a better and cheaper iron chelator as compared to the daily subcutaneous regimen;