Objective: To assess the effects of chronic erythrocyte transfusions on prevalence of sonographic incidence of organ damage in children with sickle cell anemia (SCA). Study design: Children (N = 148; mean age, 13.0 years) with SCA, receiving chronic transfusions (average, 7 years), underwent abdominal sonography at 25 institutions. After central imaging review, spleen, liver, and kidney measurements were compared with published normal values. Potential relations between ultrasound, clinical, and laboratory data were explored via analysis of variance, Student t test, and Cochran-Mantel-Haenzel tests of non-zero correlation. Results: Average spleen length was similar to normal children, but over one-third had spleen volumes >300 mL, 15 had previous splenectomy for splenomegaly, and 24 had abnormal splenic echotexture. Two-thirds had hepatobiliary disease; 37 had prior cholecystectomy, 46 had gallstones, and 16 had gallbladder sludge. Gallbladder disease correlated with older age (P =.002), longer liver length (P <.001), longer duration of transfusions (P =.034), and higher total bilirubin (P <.001). Liver (P <.001) and renal lengths (P ≤.005) were larger than published norms. Conclusions: In children with SCA, long-term transfusion therapy may not prevent development or progression of abdominal organ dysfunction.