To estimate the cost-effectiveness ratio of surfactant rescue treatment of premature infants with respiratory distress syndrome (RDS) who are covered by the Medical Insurance for a New Generation. A cost-effectiveness evaluation was conducted from the third-payer perspective. Comparisons were made between the use of bovine surfactant (BS) therapy and without BS therapy. A decision tree model with a lifetime horizon was used where the measurements of effectiveness were life years gained (LYG) and quality-adjusted life years (QALYs). A 5% discount rate was considered for costs and health outcomes. All costs are expressed in Mexican pesos 2009. Incremental cost-effectiveness ratios (ICER) were MXN$136,670 per LYG and MXN$125,250 per QALY. Surfactant therapy was confirmed as a cost-effective strategy in accordance with World Health Organization criteria of three per capita gross domestic product (GDP) per QALY in premature infants with RDS in Mexico.