Objective: To evaluate the in-hospital outcome of moderate to severe COVID-19 patients admitted in High Dependency Unit (HDU) in relation to invasive vs. non-invasive mode of ventilation. Methods: In this study, the patients required either non-invasive [oxygen ≤10 L/min or >10 L/min through mask or nasal prongs, rebreather masks and bilevel positive airway pressure (BiPAP)] or invasive ventilation. For analysis of 30-day in hospital mortality in relation to use of different modes of oxygen, Kaplan Meier and log rank analyses were used. In the end, independent predictors of survival were determined by Cox regression analysis. Results: Invasive ventilation was required by 15.1% patients while 84.9% patients needed non-invasive ventilation. Patients with evidence of thromboembolism, high inflammatory markers and hypoxemia mainly required invasive ventilation. The 30-day in hospital mortality was 72.7% for the invasive group and 12.9% for the non-invasive group (1.8% oxygen <10 L/min, 0.9% oxygen >10 L/min, 3.6% rebreather mask and 4.5% BiPAP). The median time from hospital admission to outcome was 7 days for the invasive group and 18 days for the non-invasive group (P<0.05). Age, presence of co-morbidities, number of days requiring oxygen, rebreather, BiPAP and invasive ventilation were independent predictors of outcome. Conclusions: Invasive mechanical ventilation is associated with adverse outcomes possibly due to ventilator associated lung injury. Thus, protective non-invasive ventilation remains the necessary and safe treatment for severely hypoxic COVID-19 patients.