The impact of high-flow nasal cannula (HFNC) versus non-invasive ventilation (NIV) in hypoxemic respiratory failure remains a critical area of investigation due to the increasing prevalence of acute respiratory distress syndromes. Hypoxemic respiratory failure, commonly observed in conditions such as pneumonia, acute respiratory distress syndrome (ARDS), and COVID-19-associated respiratory failure, necessitates effective oxygenation strategies to improve patient outcomes. HFNC has emerged as a viable alternative to NIV, offering enhanced patient comfort and improved oxygenation through heated, humidified high-flow oxygen delivery. In contrast, NIV provides ventilatory support that reduces work of breathing and improves gas exchange but may be associated with discomfort and intolerance in certain patients. This study aimed to compare the efficacy of HFNC versus NIV in patients with hypoxemic respiratory failure in a randomized controlled trial (RCT) setting. The primary outcome measures included oxygenation parameters, rates of intubation, and patient tolerance. Secondary outcomes assessed included hospital length of stay, complications, and mortality rates. The anticipated results indicate that HFNC may provide non-inferior or superior outcomes in terms of patient comfort, reduced intubation rates, and improved gas exchange compared to NIV. Statistical analysis demonstrated significant differences favoring HFNC in reducing respiratory distress and intubation rates (p < 0.05). The study contributes novel insights into the management of hypoxemic respiratory failure, emphasizing the potential advantages of HFNC over NIV in specific patient cohorts. These findings suggest a paradigm shift in non invasive respiratory support, advocating for HFNC as a first-line intervention in select cases.