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OBJECTIVE: To study the efficacy of pulmonary surfactant (Exosurf) in the prevention of the neonatal respiratory distress syndrome (RDS) in preterm infants. METHODS: A prospective clinical trial was conducted. To prevent RDS, a single dose of pulmonary surfactant (Exosurf) was administered intratracheally in 25 preterm infants at a high risk of developing RDS as the prophylaxis group, and another 25 preterm babies who received no surfactant administration formed the control group. RESULTS: The preterm infants in the prophylaxis group received a prophylactic dose of surfactant (67.5 mg/kg) within 0.25 to 6 hours (3.4±1.9 hours) after delivery. Oxygenation in these babies was markedly improved and their clinical symptoms were relieved after the administration of surfactant. The durations of supplemental oxygen administration, assisted ventilation and hospitalization in the prophylaxis group, were (9.5±6.9) days, (2.6±3.8) days and (40.8±17.8) days respectively, which were significantly shortened compared with those of the control group (P<0.05). Although the incidence of RDS and mortality in the prophylaxis group (20% and 8%) seemed to be lower than those of the control group (32% and 12%)，there was no statistical differenc (P>0.05). CONCLUSIONS: Prophylactic administration of surfactant can improve oxygenation, relieve symptoms, and shorten the duration of supplemental oxygen administration, assisted ventilation and hospitalization. It has a relief effect on RDS in preterm infants.