Background: Noninvasive mechanical ventilation (NIV) decreases the need for endotracheal intubation (ETI) and also decreases mortality in severe acute exacerbation of COPD (AECOPD). Objective: The aim of the current study is to assess determinants of NIV effectiveness in patients with COPD exacerbation. Patients and methods: Our study was a cross-sectional comparative study. A total 100 patients with AECOPD were included in this study. Patients were admitted to the Respiratory Intensive Care Unit (RICU) in Minia Cardiothoracic University Hospital. All patients were evaluated at the time of admission, at the start of NIV, after 1 hour (hr) of NIV and at the end of NIV. This evaluation included heart rate, respiratory rate, systolic blood pressure, diastolic blood pressure, and arterial blood gases (ABG) which include PaO2, PaCO2, PH, HCO3, as well as PaO2 /FiO2 ratio. Results: Patients were divided into 2 groups; 85 (85%) patients improved with NIV (success group, Group I) and 15 (15%) patients failed NIV and were intubated (Group II). PH, PO2, as well as PCO2 revealed significant improvement after 1 hr, which persisted till the end of the study in the success group. Clinical data including heart rate, respiratory rate, systolic blood pressure, and diastolic blood pressure showed significant difference between the two groups at time of hospital admission and the initiation of NIV. After 1 hr, these variables showed significant improvement in the success group that continued till the and at the end of the study. Also, PaO2/FiO2 ratio showed a significant improvement in the success group after 1 hr of NIV. Multivariate analysis showed PH <7.26 and RR ≥ 35 (at hospital admission) are predictors of failure of NIV. Conclusion: Clinical parameters including HR, RR and blood pressure, as well as ABG, could predict success of NIV in patients with AECOPD. Improvement in these parameters within 1 hr of NIV could be a good predictor of success.