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Objectives: To conduct a prospective study to evaluate the lipid profile in children and adolescents with beta-thalassemia intermedia and major, and to examine the contribution of different factors to hypocholesterolemia observed in these patients., Study Design: Demographic, clinical, and laboratory data were prospectively obtained from patients with beta-thalassemia intermedia (n = 9) and major (n = 47). Lipid profiles were also determined in a control group of healthy children (n = 18). Lipid values of beta-thalassemics and controls were compared and the relationships between lipid levels and different covariates were determined., Results: beta-thalassemia intermedia patients had significantly lower total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) compared with beta-thalassemia major and controls (P <.001). With regression analysis, serum lipid levels (TC, HDL-C, and triglycerides) correlated with diagnosis (beta-thalassemia major or intermedia) but not with age, sex, hemoglobin, or ferritin. LDL-C was influenced by both diagnosis and ferritin levels., Conclusions: Children and adolescents with beta-thalassemia intermedia have significantly lower cholesterol levels than patients with beta-thalassemia major. This is related to their disorder and not influenced by age, sex, hemoglobin, or ferritin levels. In these patients, needless investigations for hypolipidemia should be avoided.