〔Abstract〕 Objective To evaluate the value of lung ultrasound and diaphragm ultrasound combined with N terminal pro B type natriuretic peptide (NT–proBNP) in predicting the failure of mechanical ventilation withdrawal. Methods 90 patients with endotracheal intubation mechanical ventilation > 48 hours treated in the Eighth Affiliated Hospital of Sun Yat-sen University from October 2019 to October 2021 were included. After the start of spontaneous breathing trial (SBT), the lung ultrasound score (LUS) and diaphragmatic thickening fraction (DTF) were measured with bedside ultrasound, and the NT–proBNP was detected at the same time. Patients who successfully passed the SBT for 1 hour were removed the endotracheal intubation and observed, the outcome of weaning and the predicted values of LUS, DTF and NT–proBNP were observed. Results Among the 90 patients, 68 cases (75.6%) were successfully deactivated, and 22 cases (24.4%) were failed. Binary logistic regression analysis showed that LUS, DTF and NT_x0002_probNP were all related to the withdrawal failure of patients with invasive ventilation (P < 0.05). Receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of LUS, DTF and NT-proBNP for predicting disconnection failure were 0.73, 0.87 and 0.82 respectively. The thresholds for predicting disconnection failure were LUS ≥ 18 points, DTF ≤ 32 % and NT-proBNP ≥ 1374 pg·mL-1, respectively. The AUC of the three indexes was 0.90, which was higher than that of the single index, and its sensitivity and specificity were 91% and 78% respectively. Conclusion Lung ultrasound, diaphragm ultrasound and NT–proBNP can predict the failure of weaning well, and the prediction efficiency of the combination of the three is higher than that of single.