Objective To explore the prevention and treatment effects of either antenatal corticosteroids (ACS) or postnatal pulmonary surfactant (PS) alone or the combination of both ACS and PS on neonatal respiratory distress syndrome (RDS). Methods One hundred and forty - three cases of RDS admitted to our neonatal intensive care unit ( NICU ) from Jan. 2003 to Jan. 2007 were selected, and divided into 4 groups:group 1 received both ACS and PS (n =36) ;group 2 only received ACS(n =33) ;group 3 only received PS (n =39) ;group 4 didn't receive both ACS and PS (n =35). The clinical parameters like sex,gestational age,birth weight,mode of dellvery,associated maternal risk factors, the Apgar score,the need of resuscitation at the time of delivery and associated perinatal complications of the babies were analyzed.The relation between the 4 groups regarding the different modes of supplemental oxygen use ( nasal prong and head box), continuous positive airway pressure (CPAP) ,the need of mechanical ventilator (MV) ,the mean NICU days to cure from the RDS and finally the treatment outcomes were compared. Results There were no significant differences between the 4 groups with regards to their general features and clinical parameters( P > 0.05 ). There was a significant difference between the groups regarding the mean hour requirement of the supplemental oxygen ( nasal prong and head box), CPAP and MV. Nasal prong : The mean hour for each group was ( 75.81 ± 15.63 ), ( 130.09 ± 27.32 ),(150.67 ±28.59) ,( 174.32 ± 25.92) h,respectively (P=0.041). Head box: The mean hour for each group was (37.16 ±5.51) ,(55.29 ±11.71 ), (62.69 ±12.39 ), ( 100.75 ± 28.10 ) h, respectively ( P = 0.047 ). CPAP: The mean hour for each group was ( 24.33 ± 4.41 ),(27.44 ±4.47), (26.53±3.13 ), (56.50 ± 5.50 ) h, respectively ( P = 0. 005 ). MV: The mean hour for MV use for each group was ( 56.12 ±15.65 ), ( 110.19 ± 21.59 ), ( 127.79 ± 26.36 ), ( 156.61 ± 12.92 ) h, respectively ( P = 0. 009 ). The mean number of days in NICU to recover for each group was ( 15.89 ± 1.29 ), (21.61 ± 2.30 ), ( 28.31 ± 3.40 ), ( 32.73 ± 4.57 ) d, respectively ( P = 0 ). The complete cure rate for each group was 63.89%, 51.52% ,35.90% ,20. 0% ,respectively. It shown a significant difference (P =0. 005 ) among the 4 groups regarding treatment outcomes. Conclusions ACS and PS combined therapy is the most effective therapy for the prevention of RDS,followed by ACS therapy alone,then PS therapy alone,and no ACS/no PS therapy is the least effective.