Background: The use of invasive mechanical ventilation (MV) sometimes is an inevitable lifesaving step in management of critically ill patients. However, being associated with numerous complications, the invasive MV should be discontinued at the earliest possible time in the course of a patient's illness. Successful, timely weaning and extubation of critically ill patients has a considerable bearing on ultimate outcome. Objective: To evaluate the use of transthoracic echocardiography (TTE) and tissue Doppler imaging (TDI) in predicting failure of weaning of critically ill patients from mechanical ventilation due to cardiac origin. Patients and Methods: This study was done on ninety adult patients of both sexes admitted to the units of anesthesia intensive Care Department at Al-Hussein and Bab El-Sharia Hospitals, Al-Azhar University. The included patients were selected from those who were mechanically ventilated for more than 48 hours, TTE & pulsed tissue Doppler imaging (TDI) performed at the lateral mitral annulus just before initial spontaneous breathing trial and E/E' index should be calculated  in patient eligible for weaning. The study conducted during the period from December 2018 to December 2020. Results: Cardiogenic pulmonary edema was the most frequent cause (65.4%) for weaning failure among the studied population and mainly among patients with systolic dysfunction. There were no statistical significant differences between successfully weaned and failed weaning groups regarding demographic data, positive pressure used for ventilation, and the use of diuretics within 48 hours before the SBT. Conclusion: TTE and pulsed wave tissue Doppler imaging performed at the lateral mitral annulus before initiating the spontaneous breathing trial (SBT) were considered a useful bedside tool helping predict failure of weaning from mechanical ventilation in critically ill patients due to cardiac origin.