OBJECTIVES: Deferasirox is a recently approved once-daily oral chelator that has been shown to produce reductions in liver iron concentrations and serum ferritin similar to those with infusional deferoxamine. The cost-effectiveness of deferasirox vs deferoxamine in β-thalassemia major patients have has not been examined. METHODS: A Markov model was used to estimate the total additional lifetime costs and quality-adjusted life years (QALYs) gained with deferasirox versus deferoxamine in patients with β-thalassemia major and chronic iron overload from blood transfusions. Patients were assumed to receive prescribed dosages of deferasirox and deferoxamine that have been shown to be similarly effective in such patients. Compliance with deferoxamine as well as costs of deferoxamine administration and complications of iron overload were based on analyses of health insurance claims data of transfusion-dependent thalassemia patients. Probabilities of complications of iron overload and death by level compliance with chelation were estimated using data from published studies. Because data on compliance with deferasirox in typical clinical practice are unavailable, we used published data on compliance with the oral chelator deferiprone vs deferoxamine. Utilities (weights representing patient quality of life) were based on a study of patient preferences for oral vs infusional chelation therapy, as well as published literature and assumption. A US healthcare system perspective was employed. RESULTS: Deferasirox results in a gain of 3.9 QALYs per patient at an additional expected lifetime cost of $133,321 per patient. Cost-effectiveness is $33,792 per QALY gained. Cost-effectiveness is sensitive to the estimated costs of deferoxamine administration and the quality of life benefit associated with oral vs infusional therapy and is more favorable in younger patients. CONCLUSIONS: The cost-effectiveness of deferasirox vs deferoxamine in patients with transfusion-dependent β-thalassemia is within the range considered generally-accepted in the United States.