Background: A domestic surfactant preparation has been used in China for a number of years. However, as for other surfactant preparations, there is debate among neonatologists regarding the optimal dose, mode of administration, and the best time of intervention. Objective: To evaluate whether prophylactic administration of surfactant is superior to early treatment in preterm infants < 32 weeks with a high risk of respiratory distress syndrome (RDS). Methods: We prospectively compared small premature infants (< 32 weeks) receiving 70 mg/kg bovine surfactant within 30 minutes after birth (prophylactic group, N = 116) with infants who received surfactant therapy for established RDS (early treatment group, N = 91). The primary outcome assessed was the incidence of RDS. The secondary outcomes assessed were severity of RDS, mortality, and bronchopulmonary dysplasia morbidity. Results: Compared with the early treatment group, the prophylactic group had a significantly better PaO2 (at 1 hour, 4 hours, and 12 hours postdose, respectively), better a/APO(2) (at 1 hour, 4 hours, 12 hours, and 24 hours postdose, respectively), lower PaCO2 (at 1 hour postdose), and a significantly decreased need for mean airway pressure (MAP) and FiO(2) on ventilation (p < 0.05). The prophylactic group had shorter durations for mechanical ventilation and supplemental oxygen compared with the early treatment group (p < 0.01 and p < 0.05, respectively). The incidence of RDS was comparable between the groups; however, the prophylactic group had a significantly lower incidence of severe RDS and significantly lower rate of repeated doses of surfactant than the early treatment group (p < 0.05). The incidences of bronchopulmonary dysplasia and patent ductus arteriosus were also lower in the prophylactic group than the early treatment group (p < 0.05). The two groups were comparable in mortality rate. Conclusion: In preterm infants under 32 weeks' gestation, prophylactic use of a domestic surfactant preparation is better than early surfactant treatment in improving pulmonary status and in decreasing the incidence of severe RDS and duration on mechanical ventilation. Copyright (C) 2016, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC.