To evaluate the incidence, clinical course, and possible risk factors of cholestasis in very low-birth-weight infants. A retrospective study of 143 very low-birth-weight infants was performed. Cholestasis was defined as direct-reacting bilirubin > 2 mg/dL for more than 14 days. The clinical course of cholestasis was described, and perinatal risk factors were evaluated for associations with the development and severity of cholestasis. Cholestasis was present in 31 infants (21.7%). The mean (SD) age of onset was 30.3(15.3) days after birth or 26.0 (15.6) days after receiving parenteral nutrition, and the mean (SD) duration was 77.1 (33.8) days. In half of the cholestatic infants, bilirubin continued to rise after discontinuing parenteral nutrition. One infant developed signs of liver cirrhosis and died, two infants died with progressive cholestasis, while the other 28 patients recovered. Analysis of risk factors revealed that birthweight and duration of fasting significantly correlated with the development of cholestasis, and that sepsis significantly influenced the severity of cholestasis. Cholestasis is a common complication of extreme prematurity. The clinical course seems benign but long-term sequelae are unknown. Immature liver function and absence of stimuli for intestinal motility and hormonal secretion predispose to decreased bile flow, while sepsis further impairs hepatic ductular secretion and aggravates cholestasis.