Objective To investigate the value of cardiopulmonary ultrasound in predicting the withdrawal of mechanical ventilation in neonates with meconium aspiration syndrome (MAS) and persistent pulmonary hypertension of the newborn (PPHN). Methods The clinical data of patients diagnosed with MAS and PPHN who were treated with mechanical ventilation in neonatal intensive care unit from December 2022 to December 2023 were retrospectively analyzed. Results A total of 60 patients (36 boys and 24 girls) were included, and the average gestational age was (37.7±2.0) weeks. There were 12, 22 and 26 cases of mild, moderate and severe pulmonary hypertension, respectively. According to the weaning outcomes, 42 patients were included in the successful group and 18 were included in the failed group. When the ventilator was removed, compared with the failed group, the successful group had lower pulmonary ultrasound scores, lower pulmonary artery systolic pressure and higher left ventricular ejection fraction, with statistical significance (P<0.05). In both the successful and failed group, there were statistically significant differences in lung ultrasound scores, PaCO₂, PaO₂, OI, pulmonary artery systolic pressure, peak displacement of tricuspid annular contraction, peak velocity of tricuspid annular contraction, and left ventricular ejection fraction between before mechanical ventilation and the day of withdrawal (P<0.05). Multivariate logistic regression analysis showed that elevated pulmonary ultrasound score and pulmonary artery systolic pressure were independent risk factors, while elevated left ventricular ejection fraction was independent protective factor for withdrawal failure of patients with MAS and PPHN (P<0.05). The lung ultrasound score, pulmonary artery systolic pressure, left ventricular ejection fraction, and the combination of the three indicators had AUC values of 0.85, 0.76, 0.75, and 0.93 for the purpose of predicting withdrawal failure of mechanical ventilation in neonates with MAS and PPHN, respectively. Conclusions Cardiopulmonary ultrasound has a certain value in predicting the withdrawal of mechanical ventilation in neonates with MAS and PPHN. In clinical practice, pulmonary ultrasound score, pulmonary artery systolic pressure and left ventricular ejection fraction can be combined with clinical manifestations for comprehensive evaluation.