We report surgical reversal of intractable total parenteral nutrition (TPN)-associated cholestasis refractory to conservative treatment in 9 premature infants. Indications for TPN were poorly tolerated enteral feedings in all patients. Five patients had undergone gastrointestinal operations; in addition, 7 of the 9 patients had had bacterial sepsis. The median duration of TPN was 28 days (range, 20 to 50 days). The median duration of preoperative full enteral nutrition after weaning from TPN was 34 days (range, 16 to 95 days). All patients had progressive conjugated hyperbilirubinemia, no excretion of Tc-labeled HIDA to the biliary tree and duodenum, and markedly elevated liver enzyme values. Intraoperative cholangiography showed normal biliary anatomy in all cases; in addition, 2 patients had gallbladder stones. Bile was hyperviscous in all patients and contained biliary sludge in 4. The biliary tree was irrigated and the liver biopsied in all patients. The gallbladder was removed from 2 patients who had stones in the gallbladder. Liver histology was consistent with TPN-associated cholestasis in all cases, and in addition, 4 cases showed significant destruction of intrahepatic bile ducts. One patient died 2 weeks postoperatively from intracerebral hemorrhage. Jaundice completely resolved in other patients within 2 weeks. HIDA-biligraphy performed 1 to 2 months postoperatively showed normal excretion of the radioactive marker to the biliary tree and duodenum in all cases. The functional abnormality in bile excretion and bile duct motility in TPN-associated cholestasis may be reversed by irrigation of the biliary tree. Surgical intervention should be considered when cholestasis is progressive and refractory to medical management.