Background <p>Respiratory distress syndrome (RDS) is a common problem in premature infants, whose treatment with surfactant increases their survival. Surfactant does not reduce chronic complications such as chronic lung disease. Using budesonide with surfactant may reduce some of these complications. This study aimed to compare the effect of surfactant with and without budesonide on the outcomes of RDS in infants.</p> Methods <p>This double-blind, randomised control trial was conducted from September 2023 to April 2024 in the neonatal intensive care unit of Afzalipour Hospital, Kerman, Iran, on premature infants with a gestational age of less than 32 weeks with RDS requiring surfactant. Infants were randomly assigned to two groups: surfactant alone and surfactant with budesonide (30 neonates in each group). Infants were examined daily by neonatologists and the data was recorded in the study checklist by a nurse; both were unaware of the grouping. Data analysis was done using SPSS software version 26.</p> Results <p>The use of surfactant with budesonide significantly reduced the average duration of ventilation (<i>P</i> = 0.029) compared to surfactant alone. However, this treatment approach did not cause a significant difference in other outcomes, including the need for additional doses of surfactant, intraventricular hemorrhage, pneumothorax, BPD, PIE, sepsis, pulmonary and gastrointestinal bleeding, NEC, the need for inotropes, and mortality between the two groups (<i>P</i> &gt; 0.05).</p> Conclusion <p>The use of surfactant with budesonide can reduce the duration of ventilation, but has little effect on other outcomes of RDS. The long-term prognosis of this type of treatment should be followed up at the age of 2 years, and more studies are needed to clarify its effectiveness.</p>