Objective: As effects of glucocorticoids differ with respect to preparation, dose and duration, we hypothesized that a postnatal regimen of a low-dose, short-course betamethasone treatment had comparable efficacy and a better safety profile compared to the conventional high-dose, dexamethasone.Study Design: To test our hypothesis, we selected premature neonates with a birth weightp1000 g and a gestational age p29 weeks who were ventilated >10 postnatal days with an FiO 2 >0.4 and no ability to wean mechanical support for X3 consecutive days. These neonates either received twice daily dexamethasone 0.25 mg kg À1 per dose intravenously for 3 days tapered to 0.125 mg kg À1 per dose for 4 days (June 1999 to December 2000) or betamethasone 0.125 mg kg À1 per day intramuscularly once per day for 3 days (January 2001 to December 2002). Result:We found a significant reduction in FiO 2 after 3 days in both glucocorticoid treatment groups. There were no significant differences between the two treatment groups in the clinical parameters including decrease in FiO 2 , oxygenation index, mean airway pressure and percent extubation. Duration of ventilation, number of oxygen days and length of hospital stay were comparable in the two groups. Of particular interest, the betamethasone group showed fewer adverse effects, such as poor weight gain and high blood glucose, than the dexamethasone group.Conclusion: A short course of low-dose betamethasone has comparable efficacy and seemingly a better short-term safety profile compared to conventional dexamethasone treatment.