In a prospective, double-blind, placebo-controlled trial, the efficacy and safety of ursodeoxycholic acid (UDCA) was evaluated in preterm infants, in terms of its potential impact on fat absorption, advancement of enteral feeding, development of cholestasis, growth, nutritional status, and metabolic status. Although fecal fat excretion slightly decreased and achievement of full enteral feeding was earlier in the UDCA group, these differences were not significant. Interestingly, whereas serum gamma-glutamyl transferase activity increased during the parenteral nutrition period in the placebo group, we observed a constant and significant decrease in the UDCA group. This observation warrants further investigation to determine the utility of prophylactic UDCA in preventing cholestasis in infants with prolonged parenteral nutrition.