Background: The causes of weaning failure are multifactorial; they include excess mechanical load, diaphragmatic dysfunction, and weaning-induced cardiovascular disease. Aim: To investigate mitral annular plane systolic excursion (MAPSE) as a predictor of weaning failure and its correlation with death and hospital stay. Patients and methods: This investigation was a prospective observational cohort investigation that involved fifty cases who have been admitted to the Critical Care Medicine Department at Cairo University Hospitals (Kasr Al Aini Hospitals) between January 2019 and December 2020. Results: Weaning attempts were successful for less than half of the participants (48%). and failed in 52% of the participants, as reintubation was needed for one-third (32%) of patients and non-invasive ventilation within 48 hours of extubation was used for 20.0% of the patients. Ventilator days ranged between 2.00 and 28.00 days, and their mean ±SD was 11.98±6.56 days. Regarding days of ICU stay, they ranged between 4.00 and 30.00 days, with a mean ±SD of 16.30±7.48 days. There was a significant variance among failed weaning & cases treated with vasopressors (P-value <0.05), and a highly significant variance among weaning and mortality, as mortality was lower in cases who were successfully weaned (P-value less than 0.001). Conclusion: The study suggests that reduced MAPSE can indicate weaning failure and death, while higher values indicate shorter ICU stays. The RSBI and SOFA scores predict successful weaning, whereas the SOFA and APACHE II scores indicate death.