Background:  Lung ultrasonography (LUS) and transthoracic echocardiography (TTE) are reliable tools to predict weaning failure. Objectives: This study aimed to identify the predictive value of the combined use of pulmonary ultrasonography and TTE in weaning failure. Patients and Methods: Our work was a prospective cohort observational study. LUS and TTE were performed before (basal) and 30 min after the trial of spontaneous breathing (SBT) (120 min) for fifty patients of both sexes, aged more than 18 years old and had postoperative mechanical ventilation. SBT was done using pressure support (PS) mode (PEEP 5 cmH2O, PS 7 cmH2O, and FIO2 0.5). Results: LUS score was significantly increased after SBT in group WF (weaning failure) [21±2.7 vs group WS (weaning success) 15.2±2.9, p-value < 0.001]. E/A and E/Ea ratio had a significant increase after SBT in group WF [1.4±0.3 vs group WS 1.2 ± 0.2., p = 0.002], group WF [15.7±5.4 vs group WS 8.4±2.5, p < 0.001] respectively. The LUS score and E/Ea ratio after SBT had a high value of the area under the curve in the analysis of the ROC curve  (0.917 & 0.904) respectively. The combined use of the LUS score and E/Ea ratio had a high predictive value in weaning failure with 94.1% specificity, and 96.2% positive predictive value. No difference regarding EF, CVP, and fluid balance. Conclusion: In postoperative mechanically ventilated patients, the combination of LUS and TTE was highly predictive of weaning failure.