Background: High Flow Nasal Cannula appears to be a promising alternative to standard oxygen and non-invasive ventilation for treating patients with hypoxemic acute respiratory failure. Therefore, the present study aimed to evaluate the effect of high-flow nasal cannula versus non invasive ventilation on critically ill patient outcomes. Research hypotheses: high-flow nasal cannula is expected to be more effective than non-invasive continuous positive airway pressure in reducing the length of stay, mortality rate, and post-extubation complications. A comparative, Descriptive research design was used. The study was conducted in ICUs of the anesthesia department at Assuit Main University Hospital. A purposive sample of 60 adult male and female patients who were aged (18-60 years) was included in the study and they were assigned into two groups (HFNC and NIV). Five tools were used to gather data, I: Patient assessment sheet, II: Glasgow coma scale (GCS), III: Dyspnea Visual Analogue Scale (D-VAS), IV: Device-related discomfort visual analogue scale and V: Clinical outcomes assessment sheet. Results: revealed that half of the patients in both the HFN and NIV (CPAP) groups stayed in the hospital for 6-10 days. Regarding patient progress, there is a statistically significant difference between both groups, with patients using the HFN protocol showing greater improvement than patients using the CPAP protocol. Conclusion: The patient in HFN protocol shows improvement in the level of progress than NIV (CPAP). Recommendations: High-Flow Nasal Cannula may serve as an alternative treatment for hypercapnic respiratory failure, particularly for patients who do not tolerate Non-Invasive Ventilation well.