To explore the clinical effects of less invasive surfactant administration (LISA) via a gastric tube on the treatment of respiratory distress syndrome (RDS) in premature infants aged 32 to 36 weeks.A total of 97 premature infants with RDS admitted to the Children's Hospital of Shanxi from February 2017 to January 2018 were randomly divided into LISA (47 cases) and (intubation-surfactant-extubation,) INSURE groups (50 cases). In the LISA group, 6F gastric tubes were inserted into the trachea through direct laryngoscopy under nasal continuous positive airway pressure (NCPAP), and pulmonary surfactant (PS) was injected. In the INSURE group, PS was injected via tracheal intubation and NCPAP was performed after extubation. The incidence of technical-related adverse events and various complications in the two groups were observed.PS was successfully injected through gastric tube in the LISA group. There were no significant differences in reflux, asphyxia, bradycardia (<100beats/min), apnea, FiO2, changes in PaO2 and PaCO2 at 1 hour post-treatment between the groups. During the course of administration, blood pressure and SpO2 in the LISA group were more stable, and significant differences between the 2 groups were observed. However, no significant differences in the complications and outcomes between the 2 groups occurred.The LISA technique can be used to treat premature infants with RDS aged 32 to 36 weeks with stronger spontaneous breathing ability. Further clinical studies are required to determine the optimal strategy of LISA administration and the most profitable patient population. © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.