OBJECTIVES: To estimate the average (CER) and incremental (ICER) cost-effectiveness ratios of surfactant rescue treatment of premature infants with Respiratory Distress Syndrome (RDS) who are covered by the New Generation Medical Insurance . METHODS: A cost-effectiveness evaluation was conducted from the perspective of the Mexican Ministry of Health (SSA). The comparisons were between bovine surfactant therapy and the alternative of not using it. A decision tree model with a two-year time horizon was used, where the measurements of effectiveness were life years gained (LYG) and quality adjusted life years (QALY). The effectiveness figures are taken from a systematic review, the resource usage patterns were obtained from data registered in the SSA hospital files on care, and costs from official sources in SSA 2009. A 5% discount rate was considered for costs and health outcomes. Deterministic and probabilistic analyses were conducted. RESULTS: ICER ratios for surfactant therapy per LYG and per QALY were $61,392 and $62,110, respectively. CONCLUSIONS: Surfactant therapy was confirmed as a cost-effective strategy, in accordance to WHO criteria of 3 Per-capita GDP per QALY in premature infants with RDS in Mexico.