Neonatal respiratory distress is a common problem in preterm infants. The application of CPAP is widely used in neonatal units as a primary mode of respiratory support for respiratory distress. However, discomfort, nasal injuries, and fixation difficulties have been reported as obstacles when applying CPAP. High velocity nasal insufflation (HVNI) may serve as an alternative to CPAP. Trials are needed to evaluate the effectiveness of HVNI in reducing the incidence of respiratory distress. The aim of this study is to compare the clinical effectiveness and safety of HVNI as an alternative therapy to CPAP in premature infants with moderate respiratory distress. This study is a prospective, non-inferiority, randomized, unblinded controlled trial to compare the efficacy of HVNI and CPAP. The subjects were randomly allocated to receive either HVNI or CPAP according to the study protocol. They were randomly assigned using blocks of four. The completion of HVNI therapy was determined by therapeutic failure within 72 hours following enrollment, indicated by the need for intubation.

**Inclusion Criteria:**

• Preterm infants born in Cipto Mangunkusumo Hospital with gestational age (GA) less than 32 weeks or birth weight less than 1500 grams.
• Infants with moderate respiratory distress (Downe score ≤ 6) detected within 24 hours after birth.
• Parents are willing to participate in the study.

**Exclusion Criteria:**

• Infants with severe respiratory distress (Downe score ≥ 6) requiring invasive treatment in the form of mechanical ventilation, or apnea indicated by surfactant administration via endotracheal tube.
• Infants with contraindications to the use of non-invasive ventilation such as esophageal atresia, diaphragmatic hernia, air leak syndrome, and other conditions.
• Infants with respiratory distress due to non-pulmonary abnormalities.
• Infants with congenital metabolic disorders.
• Infants with congenital abnormalities that exacerbate respiratory distress.