Background: Liberation from mechanical ventilation is an essential clinical decision. Delay in identifying appropriate weaning time resulting in increased time spent on mechanical ventilation leading to more complications and increasing medical care expenses. Purpose of the study: to investigate the effect of implementing mechanical ventilation liberation nursing strategy on patients` outcomes. Design: A Quasi-experimental research design was utilized in the present study. Setting: The study was conducted in the respiratory and general intensive care units at Assiut university hospital. Patients: A purposeful sample of 70 adult male and female patients with acute exacerbation of COPD connected to mechanical ventilator for more than 48 hours were recruited. They were divided randomly into two equal groups routine care group and checklists group each 35 patients. Instruments: Three tools were utilized to obtain data relevant to this study; Ι) mechanically ventilated patients assessment sheet, ΙΙ) respiratory care-unit checklist (RCC) ventilator weaning assessment III) Patients' outcomes assessment sheet. Results: Significant number of patients on routine care group (25.7%, P = 0.001) had prolonged mechanical ventilation (>21 day). There was a significant decrease in Sequential Organ Failure Assessment (SOFA) score in the checklists group than the routine care group (3.29±2.72) versus (5.69±4.516) respectively P=0.009. Conclusion: Application of nursing strategy based on RCC for ventilation weaning assessment decrease duration of mechanical ventilation and SOFA score. Recommendations: Applying RCC for ventilator weaning preparedness assessment on different intensive care units.