OBJECTIVE Our purpose was to evaluate the efficacy and safety of ambroxol for the prenatal prophylaxis of infant respiratory distress syndrome (IRDS). METHODS This was a prospective study with 2 groups of pregnant patients with premature labor or with premature rupture of membranes at an estimated gestation between 27 to 34 completed weeks. Ambroxol treatment group consisted of 39 subjects in whom 1,000 mg of ambroxol diluted in 500 ml of 5% glucose solution was given intravenously for 4 hours once a day for 3 days, while the control group consisted of 41 subjects in whom ambroxol was not administered. Main measures included Apgar scores, clinical signs of one or more of the following: respiratory rate of > 60/min, intercostal retraction, alar flaring, expiratory grunting, cyanosis on room air and radiological evidence of IRDS. Chi-square test was used to determine the statistical significance of the results. RESULTS Tolerable maternal side effects were noted. Profile of newborns delivered were similar in both groups. Incidence of IRDS was significantly less in the treatment group (p < 0.01). CONCLUSIONS Antenatal administration of ambroxol resulted in a significant decrease in the incidence of IRDS as well as perinatal morbidity and mortality. Due to the efficacy and safety of this drug, it might be useful for the prevention of IRDS.