Surfactant therapy has revolutionized the treatment of respiratory distress syndrome (RDS) over the past few decades. Relying on a new method, the current research seeks to compare four common surfactants in the health market of Iran to determine the best surfactant according to the selected criteria. The research was a cross-sectional, retrospective study that used the data of 13,169 infants as recorded on the information system of the Iranian Ministry of Health. To rank the surfactants used, the following indicators were measured: re-dosing rate, average direct treatment cost, average length of stay, disease burden, need for invasive mechanical ventilation, survival at discharge, and medical referrals. The CRITIC (criteria importance through intercriteria correlation) method was used to determine the weight of the indicators, and MABAC (multi-attributive border approximation area comparison) was used to prioritize the surfactants. Based on the seven selected indicators in this research (re-dosing rate, average length of stay, direct medical cost per one prescription, medical referral rate, survival at discharge, disability-adjusted life years, number of newborns in need of invasive mechanical ventilation) and using multi-criteria analysis method, Alveofact was identified as the worst surfactant in infants with either more or less than 32 weeks’ gestation. So that some criteria were worse in Alveofact group infants than other groups; for example, in the comparison of the Alveofact group with the average of the total population, it was found that the survival rate at discharge was 57.14% versus 66.43%, and the rate of re-dosing was 1.63 versus 1.39. BLES (bovine lipid extract surfactant) was the best alternative for infants more than 32 weeks’ gestation, whereas Survanta was identified as best option for infants with less than 32 weeks’ gestation. Curosurf showed an average level of functionality in the ranking. This study advises the policy makers in the field of neonatal health to increase the market share of more effective surfactants based on this study and other similar studies. On the other hand, neonatal health care providers are also advised to prioritize the use of more effective surfactants if possible, depending on the clinical conditions and desired improvements.