Background: Type II respiratory failure remains a significant cause of morbidity and mortality in critically ill patients. While non-invasive ventilation (NIV) is the established standard of care, high-flow nasal cannula (HFNC) has emerged as a promising alternative respiratory support modality. Objective: To compare the clinical efficacy, safety, and patient tolerance of HFNC versus NIV in patients with acute type II respiratory failure. Methods: This prospective randomized controlled trial was conducted over 18 months in a tertiary care respiratory intensive care unit. Eighty patients with acute type II respiratory failure were randomly allocated to receive either HFNC (n=40) or NIV (n=40). Primary outcome measures included improvement in arterial blood gas parameters (pH, PaCO₂, PaO₂), respiratory rate, heart rate, and treatment failure rates. Secondary outcomes included patient comfort scores, complications, duration of respiratory support, intensive care unit length of stay, and in-hospital mortality. Results: Both groups demonstrated significant improvement in arterial blood gas parameters at 1, 6, 12, and 24 hours. The NIV group showed faster correction of hypercapnia and respiratory acidosis at 1 hour (mean PaCO₂: 52.3±6.8 vs 58.7±7.2 mmHg, p