Rationale: Patients who fail noninvasive ventilation are generally intubated and are then subjected to complications of invasive mechanical ventilation. With trans-tracheal open ventilation, ventilator support is delivered through an uncuffed small bore minitracheostomy tube, which eliminates pooling of secretions above the cuff and thus reduces the risk of tracheo-bronchial microbial colonization. Objective: To compare trans tracheal open ventilation (treatment group) with conventional invasive ventilation (control group) in patients with exacerbation of chronic obstructive pulmonary disease who initially failed noninvasive ventilation. Methods: Patients were randomized to receive trans-tracheal open ventilation (n=19) or conventional invasive ventilation (n=20). Measurements and Main Results: There was no difference in arterial blood gases after one and thirty hours between the two groups. Two patients receiving trans-tracheal open ventilation and 13 undergoing conventional ventilation had complications (p < 0.0001). Compared to conventional ventilation, trans-tracheal open ventilation significantly decreased both the duration of mechanical ventilation (7.6 ± 4.7 days vs. 18.6 ± 10.6 days, p < 0.0001) and length of stay in the intensive care unit (10.2 ± 4.5 days vs. 21.3 ± 9.7 days, p < 0.0001). Conclusions: Trans-tracheal open ventilation was as effective as conventional ventilation in maintaining adequate gas exchange and reducing complications, duration of mechanical ventilation, and intensive care unit length of stay.