Abstract: Objective To explore the clinical value of point of care lung ultrasound scoring (POC-LUS) combined with oxygenation index in predicting the timing of weaning from mechanical ventilation in newborns with meconium aspiration syndrome (MAS). Methods A total of 59 MAS child patients who underwent mechanical ventilation in the neonatal intensive care unit of Northern Jiangsu People's Hospital from January 2022 to December 2023 were selected. According to the weaning outcomes, the patients were divided into two groups: a successful weaning group and a failed weaning group. Their general information was collected, including gender, gestational age, birth weight, and Apgar score; heart rate (HR), respiratory rate (RR), arterial oxygen partial pressure (PaO₂), arterial carbon dioxide partial pressure (PaCO₂), pH value, and fraction of inspired oxygen (FiO₂) were recorded within 6 h before weaning. Both groups were compared for POC-LUS scores and oxygenation index, and correlation analysis was performed. ROC curves were plotted to predict the efficiency of POC-LUS scores and oxygenation index alone or their combination in predicting the timing of weaning in MAS patients. Results Among the 59 patients, 45 were in the successful weaning group and 14 in the failed group. The successful group showed significantly lower RR and POC-LUS scores than the failed group, while the oxygenation index was significantly higher (P<0.05). Correlation analysis indicated that POC-LUS scores were significantly negatively related with oxygenation index (r=-0.979, P<0.05). ROC curve analysis demonstrated that when the POC-LUS score was <38.5, the area under the curve (AUC) for predicting successful weaning reached 0.893, with a sensitivity of 0.898 and specificity of 0.786, suggesting superior efficiency to oxygenation index alone. The combination of POC-LUS scores and oxygenation index showed even higher predictive efficiency for successful weaning in MAS infants, with an AUC of 0.921, a sensitivity of 0.956, and a specificity of 0.741. Conclusions The combined use of POC-LUS scores and oxygenation index can effectively assist in predicting the success of weaning from mechanical ventilation in MAS patients, serving as an effective method for determining the timing of weaning, with high clinical promotional value.