The treatment of patients with sickle cell disease and cholelithiasis is controversial. This retrospective study assesses the outcome of preoperative transfusion and timely cholecystectomy in symptomatic sickle cell disease patients. Fourteen patients who had undergone cholecystectomy were determined to have sickle cell disease. The patients' mean age was 17.9 years. Eleven patients were female. Thirteen patients had complained of abdominal pain. Ultrasound confirmed the diagnosis of cholelithiasis in 12 of 13 patients tested. Hemoglobin before treatment averaged 7.7 g/dL. Transfusion or exchange transfusion was given to 12 patients, raising the average hemoglobin to 10.3 g/dL. Postoperative morbidity was 14%: one patient had a urinary tract infection and another a left-lower-lobe pneumonia. No sickle cell crises or deaths occurred. Postoperative hospital stay averaged 4.4 days. With judicious use of preoperative transfusion, early cholecystectomy for symptomatic gallstones was well tolerated by sickle cell disease patients and is advisable to avoid the morbid sequelae of acute cholecystitis and peroperative sickle cell crisis.