Objectives: Current guidelines for pulmonary surfactant (PS) administration in preterm infants with respiratory distress rely on clinical signs and FiO₂ thresholds. Lung ultrasound offers a promising alternative for accurately diagnosing neonatal respiratory distress syndrome (NRDS) and assessing its severity. This randomized controlled trial aimed to evaluate whether a lung ultrasound-guided strategy for NRDS diagnosis and lung ultrasound scores (LUS)-guided PS administration could improve respiratory outcomes in preterm infants (<32 weeks’ gestation), compared to conventional methods. Methods: In this non-blinded randomized controlled trial, 89 preterm infants (≤32 weeks’ gestation) with respiratory distress after birth were enrolled. Participants were randomly assigned to either the ultrasound group (PS administration based on ultrasound-confirmed NRDS and LUS criteria) or the control group (PS administration according to standard clinical signs and FiO₂ requirements). Results: The ultrasound group demonstrated a significantly lower rate of invasive mechanical ventilation (p = 0.007) and a shorter duration of ventilation (p = 0.005) compared to the control group. Furthermore, the ultrasound group required less PS (p = 0.03), received their first dose at an earlier time (p = 0.017), and experienced fewer radiation exposures both before surfactant treatment and within the first week after birth (p = 0.023 and p = 0.019, respectively). Conclusions: The integration of lung ultrasound for NRDS diagnosis and LUS-guided surfactant therapy facilitates more precise and timely PS use. This strategy reduces the need for and duration of invasive mechanical ventilation and limits early radiation exposure in very preterm infants.