Background: Iron overload is a major problem in patients with Thalassemia major. An effective and safe iron chelator protocol with high compliance rate plays an important role deciding the best treatment option in these patients. This study was done to assess the efficacy and safety of both Deferoxamine and Deferasirox in Thalassemia major patients in Kirkuk province, Iraq. Patients and methods: In this retrospective study we have included serum ferritin records of 280 Thalassemia major patients treated with two types of iron chelating therapy at Thalassemia center, Azadi teaching Hospital, Kirkuk province, Iraq. The study started since March 2012 till December 2012 and they were categorized in to two groups; First group Thalassemia major patients who had been treated with subcutaneous (SC infusion) Deferoxamine, while second group had been treated with oral Deferasirox (Exjade) with serum ferritin records of both base line and 9 month later had been compared. Most patients with relatively high serum ferritin had been treated with SC Deferoxamine. As a secondary end point, side effect profile had been analyzed in the two studied groups. Results: 173 Thalassemia major patients (mean age 11 year) treated with oral Deferasirox (Exjade) had mean decrease in their serum ferritin after 9 month was 840 ng/ml while the mean decrease in the 107 patients (mean age=17 year) treated with SC infusion Deferoxamine was (1527 ng/ml) with very significant difference between the two studied groups and (p-value = 0.0005). Abdominal cramp, nausea and vomiting, skin rash were more with oral Desferosix (Exjade) than SC Deferoxamine treated patients [52 (30%), 62 (35%), 13 (7%) versus 23 (21%), 11 (10%), 0 (0%) consecutively]. Renal impairment especially elevation of serum Creatinine to a degree requiring dose modification were found in 15 patients treated with oral Deferasirox (Exjade) while it has not been noticed in patients treated with Deferoxamine. Conclusion: In spite of less side effects and more compliance of Thalassemia Major Patients treated with Deferasirox than Deferoxamine; Deferoxamine still is more effective treatment modality than Deferasirox in decreasing serum ferritin level.