OBJECTIVES:  This study sought to determine the cost-effectiveness of Poractant Alpha (200mg/KG daily) in comparison to Beractant (100mg/KG daily) in the treatment of Respiratory Distress Syndrome (RDS) in premature infants from the Mexican Institute of Social Security (IMSS) perspective. METHODS:  A systematic review of the literature was performed to identify relevant phase-III Random Controlled Trials (RCTs) and meta-analyses on the target population. Fourteen published articles were identified and a fixed-effects meta-analysis was performed using WINBUGS. A decision tree model was designed to assess the success in terms of mortality rates associated with the treatments. The costs included were cost of the drug, Intensive-Care Unit (ICU) days and adverse events. All the costs were estimated based on Diagnosis-Related Groups and Unit Costs published yearly by IMSS, except for the cost of Poractant Alpha which was obtained from other Mexican Public Health Institutions. The time horizon was 30 days, so no time discount was needed. The health outcome was the mortality rate. The perspective of the analysis was IMSS' Perspective. A probabilistic sensitivity analysis (PSA) through Montecarlo simulations was performed. RESULTS:  Poractant Alpha was an alternative that reduced the number of ICU days compared to Beractant in almost 3 days per patient. Also, it reduced the main adverse event associated with the treatment, the Bronchopulmonary Dysplasia, from 41.5% to 21.30%. As a result, the total cost of treatment (CoT, in USD) was $65,385 and $73,500, for Poractant Alpha and Beractant, respectively. Moreover, the mortality rate was 9.0% for Poractant Alpha and 16.7% for Beractant. These results were robust under uncertainty, in more than 85% of the cases. CONCLUSIONS:  Poractant Alpha is a dominant strategy over Beractant for the treatment of the RDS in premature infants from the IMSS Perspective. These results were robust under uncertainty.