Aims: To assess the efficacy of vaginal micronized natural progesterone as a tocolytic and in maintenance therapy during threatened preterm birth. Methods: Eighty-three women with symptoms of threatened preterm birth were either randomized to study groups receiving tocolytic treatment combined with intravaginal micronized natural progesterone (200 mg daily) or to a control group receiving only tocolysis. Results: Micronized natural progesterone treatment resulted in a prolonged latency period of 32.1 +/- 17.8 versus 21.2 +/- 16.3 days in the control group and heavier birth weights of 2,982.8 +/- 697.8 g versus 2,585.3 +/- 746.6 g. No significant differences were found between the groups in admission to the neonatal intensive care unit, stay at the neonatal intensive care unit, need for a mechanical ventilator, respiratory distress syndrome or neonatal sepsis. Conclusion: The treatment of threatened preterm birth with tocolytics combined with intravaginal micronized natural progesterone significantly prolonged pregnancy and increased birth weight. However, an improvement in adverse perinatal outcomes was not observed. Copyright (C) 2011 S. Karger AG, Basel