Objectives: Primary objective was to determine the diagnostic accuracy of lung ultrasound score (LUS) in predicting the need for surfactant therapy in preterm neonates (< 34 weeks) with respiratory distress. Secondary objectives were to correlate LUS with corresponding oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2), arterial/Alveolar oxygen pressure ratio (a/A]and chest x-ray (CXR) findings. Working hypothesis: LUS reflects lung aeration and will correlate with requirement of surfactant in preterm neonates with respiratory distress. It can be an accurate and timely predictor for surfactant therapy. Study design: Prospective observational study carried out at a tertiary level NICU in Western India in 2022 enrolling 100 neonates <34 weeks gestation with respiratory distress. Methodology: After initial stabilization of the neonate, LUS was performed and baseline parameters noted. Surfactant was administered as per 2019 European guidelines and LUS was repeated after 6 hours. Results: The mean gestation of enrolled neonates was 31.06 +/- 2.12 weeks and the mean birthweight was 1412 +/- 391 g. Out of 100 neonates, 40 required surfactant therapy. The cutoff LUS for surfactant therapy was 7 (area under curve [AUC] 0.977; 95% CI, 0.947-1; P < 0.001; with sensitivity 93.33%, specificity 92.5%, PPV 94.92%, NPV 90.24%) and the cutoff LUS for second dose of surfactant was 10 (AUC 0.964; 95% CI, 0.913-1; P < 0.001. The score decreased by an average 3.24 (2.44 - 4.05) after 6 hours of first dose and correlated significantly with SpO2/FiO2 ratio (-0.750), a/A ratio (-0.650) and CXR findings (0.801). Conclusion: LUS ≥ 7 can be considered an accurate marker for surfactant replacement therapy.