BACKGROUND One of the most common complications in infants under parenteral nutrition treatment is parenteral nutrition-associated cholestasis (PNAC). The etiology of PNAC is thought to be multifactorial. The aims of this study were to evaluate the risk factors for PNAC in our neonatal intensive care unit and determine useful predictors. METHODS This study enrolled premature infants (gestational age <36 weeks) who were admitted to our neonatal intensive care unit and treated with parenteral nutrition infusion for at least 2 weeks between January 2004 and January 2007. Multiple possible risk factors were analyzed by a retrospective review study design. PNAC was defined as direct bilirubin greater than 1.5 mg/dL during parenteral nutrition. RESULTS A total of 62 premature infants with prolonged course of parenteral nutrition were eligible for this study; 11 (17.74%) of the infants developed PNAC. There were significant differences in terms of gestational age, birth body weight, duration of parenteral nutrition, septic episodes, and average energy intake during the 2nd and 3rd weeks of life between infants with cholestasis and those without cholestasis. Of these risk factors, the duration of parenteral nutrition was most significant after multivariate logistic regression analysis. CONCLUSIONS Young gestational age, low birth body weight, more sepsis episodes, and long duration of parenteral nutrition were significant risk factors for PNAC in our study. Low energy intake during the 2nd and 3rd weeks of life is a predictor for PNAC.