BACKGROUND Hemoglobin E beta-thalassemia (beta-thalassemia/Hb E) has a variable severity, and the cost of treatment has not been well studied. The aim of this study was to analyze the societal cost of caring for children with beta-thalassemias in Thailand. The study was designed as a prevalence-based cost-of-illness analysis in a societal perspective. Medical records from three public hospitals of children aged 2-18 years with beta-thalassemia/Hb E and homozygous beta-thalassemia were reviewed for direct medical cost determination. For direct non-medical cost and indirect cost, a family member was interviewed. RESULTS It was found that 201 patients with beta-thalassemia/Hb E (91%) and homozygous beta-thalassemia (9%) were recruited for this study. Ninety-two (46%) were severe thalassemia and 109 (54%) were mild to moderate severity. The annual average cost of treatment was US$950; 59% was direct medical cost, 17% direct non-medical cost, and 24% indirect cost. The costs were differentiated by some potential predictors. Significant predictor variables were: hospital, health insurance scheme, blood transfusion pattern, and iron chelation drug use. CONCLUSIONS The average annual cost per patient was calculated, and the cost model was estimated. These would be applied for national planning, economic evaluation of treatment and prevention interventions, and budget impact analysis.