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Objective: To discuss the predictive value of lung ultrasound score (LUS) for the use of mechanical ventilation (MV) and pulmonary surfactant (PS) in the preterm infants with late-onset respiratory distress syndrome (RDS). Methods: The prospective analysis was conducted on the late-onset preterm infants (gestational age 340/7-366/7 weeks) complicated with RDS; in total, 67 late-onset infants complicated with RDS were included. The infants were divided into MV group (n=36), non-MV group (n=31), PS group (n=30), and non-PS group (n=37) based on the necessity to use MV and PS within 48 h after birth. Lung ultrasound examination was performed on all the infants 2 h after admission, and before the application of PS, and the LUS for 6-zone, 10-zone, and 12-zone partitions were calculated. Receiver operating characteristic (ROC) curve for the prediction of MV and PS application in the infants with late-onset RDS were drawn by LUS with different partitions, and the predictive values of different partition methods were compared by DeLong method. Results: Compared with non-PS group, the birth weight, LUS, positive end expiratory pressure (PEEP), mean airway pressure (MAP), MAP×fraction of inspired oxygen (FiO2 )/PaO2 value, duration of mechanical ventilation, and hospital stay of the infants in PS group were increased (P<0. 05), and the ratio of PaO2/FiO2 was decreased (P<0. 01). Compared with non-MV group, the birth weight, LUS, PEEP, MAP, MAP × FiO2/PaO2 value, duration of mechanical ventilation and hospital stay of the infants in MV group were increased (P<0. 05), and the ratio of PaO2/FiO2 was decreased (P<0. 01). PEEP, MAP, and LUS were identified as the influencing factors for application of PS in the late-onset preterm infants complicated with RDS when employing 6-zone LUS to predict the application of PS [odds ratio (OR)>1, P<0. 05]. When employing 10-zone and 12-zone LUS for the use of PS, MAP × FiO2/PaO2 and LUS were the influencing factors (OR>1, P<0. 05). The area under curve (AUC) for predicting the application of PS in the late-onset infants complicated with RDS by 6-zone, 10-zone, and 12-zone LUS were 0. 909, 0. 904, and 0. 915, respectively, all showing good predictive values; the AUCs for predicting the application of MV by 6-zone, 10-zone, and 12-zone LUS were 0. 868, 0. 872, and 0. 887, respectively, all showing good predictive values as well. Conclusion: LUS can effectively predict the necessity for whether or not applying MV and PS in the lateonset infants complicated with RDS, and MAP combined with LUS can enhance the capability to predict the application of MV. [ABSTRACT FROM AUTHOR]