Choledocholithiasis can be caused by either primary or secondary bile duct stones. Although patients with sickle cell disease (SCD) are at high risk of development of pigmented gallstones due to chronic hemolysis, primary choledocholithiasis in SCD is very uncommon. The delay in the diagnosis of biliary tract pathology can occur in patients who had a prior cholecystectomy. There is a possible relationship between prior cholecystectomy and the subsequent occurrence of primary common bile duct stones, due to the higher probability of infection of the biliary system. Here, we report an unusual and severe case of multiple primary choledocholithiasis, associated with pancreatitis, in a patient with SCD, fourteen years after cholecystectomy.