Background: Bronchopulmonary dysplasia (BPD) is an important morbidity caused by neonatal lung injury due to mechanical ventilator use. Respiratory distress syndrome (RDS) is leading cause of mechanical ventilation in preterm infants. Surfactant was administrated through the endotracheal tube for management of RDS, which compels invasive mechanical ventilation. Recently, Intubation-SURfactant administration-Extubation (INSURE) and Less-invasive surfactant administration (LISA) have been introduced to avoid invasive mechanical ventilation. This study aimed to compare the effectiveness of LISA and INSURE.Methods: This single-center, retrospective study enrolled 47 newborns admitted to the neonatal intensive care unit (NICU) of the Wonju Severance Christian’s Hospital between January 1, 2017 and August 31, 2019, above a gestational age of 25 weeks, and required surfactant. The patient were divided into the LISA group and the INSURE group, and compared capillary gas analysis, oxygen saturation index (OSI), and morbidities.Results: The LISA group and the INSURE group included 34 and 13 newborns respectively. Demographic feature and OSI showed no significant differences between two groups. In the LISA group, pCO2 decreased over 1 hour(57.49±9.43mmHg), 2 hours(53.07±9.25mmHg, p=0.04) and 6 hours (46.50±8.53mmHg, p=0.01). pCO2 of the INSURE group decreased steeper within 2 hours (49.55±8.96mmHg to 39.56±6.20mmHg) in the INSURE group, however, the trend was not significant (p = 0.06). There were no significant differences in morbidities. Discussion: LISA and INSURE showed no significant differences in OSI and morbidities. Although LISA decreases pCO2 more slowly than INSURE, the difference is not statistical significant. LISA and INSURE are equally effective modalities for surfactant administration.