Minimal invasive surfactant therapy (MIST) includes the tracheal instillation of surfactant via a thin catheter for the treatment of preterm infants with respiratory distress syndrome (RDS). We aimed to evaluate the impact of MIST compared to intubation, surfactant, extubation (INSURE) technique on respiratory outcomes. A prospectively recruited cohort of preterm infants ≤32 weeks with RDS was compared against a historical cohort of infants treated with INSURE. The primary outcome was the need for mechanical ventilation within 72 hours of age and secondary outcomes the overall need and duration of mechanical ventilation, the development of bronchopulmonary dysplasia, common morbidities, and survival. Thirty-six infants treated with MIST of 29.1±2.2 weeks' gestation and 1219±238 g birthweight compared against 37 infants of 28.8±2.3 weeks' gestation and 1195±336 g birthweight treated with INSURE. A lower proportion of infants treated with MIST required mechanical ventilation within 72 hours of age compared to those treated with INSURE (11% compared 32%, P=0.042). However, no significant differences were noted regarding the overall intubation incidence, bronchopulmonary dysplasia, other morbidities, or survival. In spontaneously breathing infants ≤32 weeks with RDS, the MIST technique was associated with a lower need for intubation within 72 hours of age, but otherwise with no significant differences regarding BPD or other neonatal morbidities.