Introduction: Angiogenesis has been investigated in different kinds of anemia. However, its role as a marker of angiogenesis has not been investigated in thalassemia or sickle cell disease (SCD). Objectives: We aimed to investigate serum angiogenin level in children and adolescents with beta thalassemia or SCD and its relation to possible risk factors of angiogenesis. Materials and Methods: This study included; 32 beta-thalassemia major (beta-TM) patients aged 14.2 +/- 3.8 years, 20 beta-thalassemia intermedia (beta-TI) patients aged 14.3 +/- 4.8 years, 20 SCD patients aged 14.1 +/- 2.4 years; 8 with (HbSS) and 12 with sickle thalassemia (HbS/beta-thalassemia) and 35 age and sex-matched controls. Data collected regarding; age, sex, disease duration, blood transfusion frequency, transfusion index, chelation type and duration, CBC, Hb electrophoresis, serum ferritin and serum angiogenin level (by ELISA). Results: Angiogenin level was significantly higher in patients with SCD [250 (100-300) pg/mL] compared to beta-TM [180 (140-230) pg/mL] and controls [89 (80-103) pg/mL] (P<.001) especially those with HbSS (P=.06). There was a significant negative correlation between serum angiogenin and age of patients, age of onset and duration of chelation in beta-TM (P<.01, P<.001, P=.003) and beta-TI (P=.009, P=.03, P<.001) and with serum ferritin in beta-TI group (r=-0.573, P=.008). In SCD, angiogenin level was negatively correlated with both frequency of blood transfusion (r=-0.731, P<.001) and duration of hydroxyurea therapy (P=.017). Conclusions: High angiogenin level detected among patients with SCD may be negatively influenced by regular blood transfusion and hydroxyurea therapy, while; early onset of chelation therapy may decrease angiogenin level in beta-TM.