PURPOSE: To evaluate the association between neonatal mortality and the initial response to surfactant replacement therapy, and to examine the correlation between the response type and other prognostic factors. METHODS: Sixty-seven neonates with respiratory distress syndrome (RDS) were divided into two groups; group I (n=51) who survived and group II (n=16) who died within the first 28 days of life after one trial of surfactant therapy. We observed the serial changes of several respiratory indices within the first 24 hours following surfactant therapy and performed a multiple linear logistic regression analysis to evaluate significant prognostic factors that reflected neonatal mortality. RESULTS: In group II, fraction of inspired oxygen (FiO2), respiratory rate (RR), peak inspiratory pressure (PIP), and mean airway pressure (MAP) were significantly higher for 24 hours after surfactant therapy (P<0.05). The mean serum pH was significantly lower before and at 30 minutes and 6 hours after surfactant administration (P<0.05), but mean PaCO2 was higher (P<0.05). Ventilation index (VI) and oxygenation index (OI) were higher before and for 1 day after surfactant therapy (P<0.05), but arterial/alveolar oxygen tension ratio (a/APO2) was lower (P<0.05). In multiple linear logistic regression analysis, birthweight, MAP and VI at 6 hours and PIP at 12 hours were significant indicators of neonatal mortality after surfactant replacement therapy (P<0.05). CONCLUSION: The response to surfactant treatment within the first 24 hours may be also a significant prognostic indicator for neonatal mortality as other factors are, such as birthweight.