OBJECTIVE: To study the complications of the respiratory distress syndrome (RDS) following pulmonary surfactant (PS) replacement therapy in neonates. METHODS: Ninety-eight newboms with RDS were assigned into the PS treatment group and the control group. The former, besides the usual treatment for the control group, received PS replacement. The duration of mechanical ventilation and oxygen treatment, survival rate, length of hospitalization and incidence of complications, including ventilator associated pneumonia, patent ductus arteriosus, lung hemorrhage, air leak, intracranial hemorrhage, bronchopulmonary dysplasia (BPD) and apnea were compared between the two groups. RESULTS: There were significant differences in the ventilation time [(7.0±5.4) days vs (9.5±6.2) days, P < 0.05) ], duration of the oxygen period [(10.0 ±6.4) days vs (13.2 ±8.1), P<0.05)] and survival rate [87.0% vs 69.2%, P <0.05)] in the PS treatment group compared with the control group. Significant differences were noted in the incidence of complications between the two groups; the PS treatment group had lower incidences of air leak and ventilator associated pneumonia [(15.2% vs 32. 7 % , 44.2 % vs 23. 9 % , respectively] (both P < 0.05). There were higher rates of cases without BPD or/and intracranial hemorrhage in the survivals of the PS treatment group compared with the central group [(75.0% vs92.5%, 77.8% vs 95.0%, 58.3% vs 80.0%, respectively] (all P <0.05). CONCLUSIONS: Mechnical ventilation days and the length of the oxygen treatment period could be reduced and the survival rate could be increased by PS replacement therapy in newboms with RDS. PS replacement therapy can decrease the incidence of complications, and decrease brain and pulmonary injuries and improve the quality of life of premature newboms.