Endothelial injury is perhaps the inciting factor leading to the microangiopathic process that initiates thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS). TTP-HUS after postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is extremely rare, but potentially is life threatening. Here, we describe a case of a 23-year-old man with a history of choledocholithiasis, who developed TTP-HUS, 2 days after the onset of post-ERCP pancreatitis. It is important that physicians recognize TTP-HUS as one of the potential causes of acute kidney injury in cases of acute pancreatitis and post-ERCP pancreatitis for adult patients, especially when there is concomitant thrombocytopenia and hemolytic anemia. The early initiation of plasma exchange has a major impact on the survival and preservation of renal function. Exchange transfusion of fresh frozen plasma remains the cornerstone treatment of TTP-HUS.