Purpose of investigation: To compare single versus multiple courses of antenatal betamethasone administration with regards to the morbidity and mortality of preterm neonates. Methods: One-hundred and twenty-two women with threatened preterm labor were allocated to three different betamethasone schedules: 1) two doses of betamethasone 1 2 mg, intramuscularly, 24 hours apart (standard treatment) (n = 41); 2) standard treatment plus a third dose of 12 mg after seven days (n = 41); and, 3) standard treatment plus one dose of 12 mg every seven days until delivery (n = 40). Neonatal morbidity and mortality as well as maternal morbidity were evaluated. Results: Neonatal parameters, such as frequency of respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, sepsis and neonatal mortality were not significantly different among the three groups for both singleton and multiple pregnancies. Similarly, maternal parameters were not significantly different among the three groups. Conclusion: The administration of multiple betamethasone courses in threatened preterm labor is not superior to single courses with regards to neonatal morbidity and mortality, as well as to maternal morbidity.