Background: Sickle cell disease (SCD) is an autosomal recessive blood disorder characterized by multiple-organ involvement including the gallbladder. Subjects with SCD are prone to developing pigment gallstones due to chronic red blood cell hemolysis, increased bilirubin levels, cholecystitis, and biliary sludge.Ultrasonography is a noninvasive, readily available, and permits a fast evaluation of the gallbladder. It is useful in establishing the various patterns of gallbladder disease and volume abnormalities. Objectives: The objectives of this study were to sonographically evaluate cholelithiasis and gallbladder volume in patients with SCD and correlate the findings with age and gender. A comparison of the above parameters in sickle cell patients was also made with apparently healthy controls. Materials and Methods: This was a prospective study of 150 patients with SCD and an equal number of apparently healthy control subjects in Benin City. Each subject was sonographically evaluated for possible gallbladder stones and its volume using a 3–5 MHz curvilinear array transducer with a SonoaceX4 ultrasound machine (Medison, Seoul, South Korea). Result: The prevalence of cholelithiasis among subjects with SCD in this study was 10%. Patients with SCD had a significantly higher mean gallbladder volume (34.50 ± 20.43 cm3) compared with apparently healthy control subjects (20.39 ± 10.71 cm3; P = 0.000). Conclusion: The prevalence of cholelithiasis in SCD was shown to increase with age. There was a positive linear correlation between the incidence of cholelithiasis and gallbladder volume with age of the patient.