Objective <p>The aim of this study was to examine the predictive value of the lung ultrasound score (LUS) for successful extubation in preterm infants born at ≤25⁺⁶ weeks.</p> Methods <p>This was a single-center, prospective cohort study. Preterm infants with gestational age (GA) ≤ 25⁺⁶ weeks who received invasive mechanical ventilation (IMV) for ≥72 h were included. Lung ultrasound was performed every day. Multivariate logistic regression analysis was used to evaluate factors that predict extubation outcomes.</p> Results <p>Ninety-three infants with GA ≤ 25⁺⁶ weeks were included. The mean GA was 24.5 ± 1.2 weeks. Extubation failure occurred in 55 (59.1%) neonates, and success occurred in 38 (40.9%) neonates. The LUS was significantly lower in the successful group than in the failed group (24.0 ± 2.5 vs. 32.1 ± 3.1 <i>p</i> &lt; 0.001). Logistic regression analysis showed that LUS was an independent predictor of successful extubation (odd ratio 0.15 [95% CI 0.045–0.508], <i>P</i> = 0.002). The area under the receiver operating characteristic curve was 0.98 (<i>p</i> &lt; 0.001) for LUS, and a cutoff value of ≥ 28 had 94.6% sensitivity and 92.7% specificity in detecting extubation failure.</p> Conclusion <p>The LUS has good accuracy for predicting successful extubation in extremely preterm infants with GA ≤ 25⁺⁶ weeks.</p>