Background: Chronic obstructive pulmonary disease is a common and treatable disease. It is characterized by progressive airflow narrowing. Traditional oxygen therapy often inadequately addresses severe hypoxia or hypercapnia in COPD patients. Non-invasive ventilation became the standard treatment. However, NIV masks can cause discomfort and intolerance, leading to treatment failure. High-flow nasal cannula (HFNC) offers a promising alternative by delivering heated, humidified oxygen with precise control, improving ventilation, oxygenation, and patient comfort. This study aims to compare the efficacy of HNFC versus NIV in managing patients with hypercapnic acute exacerbation of chronic obstructive pulmonary disease. Methods: This prospective randomized controlled trial was conducted at respiratory intensive care unit at Benha University Hospital between January 2023 to January 2024.Forty patients were randomized into observational group A (use HFNC, n=20) and control group B (use NIV low- flow o2, n=20). Results: There was no significant difference between both studied groups regarding outcome after therapy; 70% of cases treated with HFNC versus 80% of cases exposed to NIV improved, and there were no differences in respiratory support duration, length of ICU and hospital stay between both groups. However, a significantly higher number of patients reported comfort with HFNC compared to NIV and the prevalence of noisiness was significantly higher in the NIV group. Conclusion: HFNC was non-inferior to NIV regarding ABG parameters during or after therapy, duration of support, ICU or hospital stay and outcome (including treatment failure and mortality). However, HFNC was better than NIV regarding patient comfort during therapy.