OBJECTIVES:  Surfactant therapy has become an integral part of the standard of care for treating premature infants with respiratory distress syndrome (RDS). Institutions that routinely treat this patient population have to select a surfactant based upon clinical and pharmacoeconomic considerations. The objectives of this study were to estimate the healthcare resource utilization, economic impact, and cost-effectiveness of poractant alfa (200 mg/kg)-treated infants versus beractant (100 mg/kg)- or poractant alfa (100 mg/kg)-treated patients for treating of RDS. METHODS:  A decision-tree model was developed to compare the healthcare resource utilization, economic impact, and cost-effectiveness of poractant alfa versus beractant. Calculating the cost of drugs and medical services was conducted according to real-world scenarios. RESULTS:  Total healthcare costs of RDS treatment with conducting comparatives for one patient for 28 days was $10980 and $11467 in the poractant alfa 100- and 200 mg/kg-group, and $11222 in the beractant 100 mg/kg-group. The cost-effectiveness ratio on the criterion "provention of death" of Number needed to treat (NNT) for the poractant alfa 100 mg/kg-group on the 28^th day of treatment was $11681, while was an increase by $141 for the poractant alfa 200 mg/kg-group and $516 for the beractant 100 mg/kg-group. CONCLUSIONS:  The use of poractant alfa (100 mg/kg and 200 mg/kg)-treated infants was more effective with acceptable the criterion "provention of death" of NNT versus beractant (100 mg/kg)-treated patients for treating of RDS.