Objective: To evaluate the efficacy of orally administered Saccharomyces boulardii (S. boulardii) on the course of hyperbilirubinemia and duration of treatment in very low birth weight (VLBW) infants. Methods: Infants with a gestational age of <= 32 weeks and birth weight of <= 1500 g were enrolled. The infants in the study group were given S. boulardii with a dose of 250 mg once a day and the infants in the control group were fed without S. boulardii supplementation. The primary outcome measurements were duration of phototherapy and levels of total bilirubin at the end of phototherapy. Results: A total of 179 infants (81 in the study group and 98 in the control group) were enrolled. The duration of phototherapy was shorter in the study group [1.9 +/- 0.86 vs. 2.6 +/- 0.9 days, p = 0.000)]. Feeding intolerance was significantly lower in the study group than in the control group (20.9% vs. 47.9%; p = 0.00). Conclusion: S. boulardii supplementation at a dose of 250 mg/day is safe for VLBW infants in the short term and effective in reducing the duration of phototherapy in VLBW infants. We suggest that it provides this effect by improving the feeding intolerance and suppressing the reabsorption of bilirubin into the enterohepatic circulation.