Background: The present study was conducted to investigate and compare the effectiveness of the minimally invasive surfactant therapy (MIST) and the INSURE technique (Intubation, Surfactant administration, and extubation) in spontaneously breathing preterm infants. Methods: Preterm infants (28-34 weeks of gestation) born with respiratory distress syndrome between April 2013 and February 2014 were randomly selected to receive 200 mg/kg of surfactant (Curosurf) using either MIST or INSURE techniques. In the MIST group, surfactant was instilled via a thin tracheal catheter (5-f) that was then removed. In the INSURE group, the infants were first intubated, administered surfactant through passing a feeding tube through the endotracheal tube, and then extubated after 30 seconds of positive pressure ventilation. Nasal CPAP for respiratory support continued in both groups after performing the procedures. The amounts of supplemental oxygen required, intensive care requirements, and outcomes were compared between the two groups. Results: The present study examined 27 infants in the MIST group and 26 in the INSURE group. The amount of oxygen required by