OBJECTIVES: Patients with β-thalassemia, sickle cell disease (SCD), and myelodysplastic syndromes (MDS) require chronic blood transfusions, which lead to iron overload and substantial morbidity (e.g., cardiac failure, diabetes, hypothyroidism, hypogonadism) and mortality. To reduce the excess iron and its deleterious effects, available iron chelation therapy (ICT) in the US includes oral deferasirox or infusional deferoxamine (DFO).  The aim of this literature review was to assess the economic burden of iron overload among US patients with β-thalassemia, SCD, and MDS.  METHODS: We identified economic evaluations of iron overload in patients with β-thalassemia, SCD and MDS that either were published in MEDLINE-indexed, English-language journals since 1999, or appeared in professional society websites and scientific meeting abstracts. We summarized and critically compared costs (adjusted to 2009 USD) from this literature. RESULTS: The majority of studies assessed direct medical costs associated with iron overload among patients with β-thalassemia and SCD, where the association was reported as costs of ICT with DFO. Annual costs of patients with complications (notably cardiac disease, diabetes, etc.) varied from $72,000 to $103,000 per patient.  Annual direct medical costs of patients undergoing ICT varied by disease—$47,000 and $74,000 per patient for β-thalassemia and SCD, respectively.  Less information was available for MDS patients. ICT accounted for ~33% of total medical costs, followed by costs for inpatient and outpatient care. Little information was available on costs incurred by untreated patients or those non-compliant with their ICT. CONCLUSIONS: The economic burden of iron overload among transfusion dependent patients with β-thalassemia, SCD, and MDS in the US is substantial. The majority of information is on SCD and β-thalassemia, while the economic burden of iron overload in MDS is not clearly elucidated.  More information is needed on the differential real-world impact of ICT choices on treatment adherence and on the economic burden overall.