Objective To compare the efficacy and safety between humidified high flow nasal cannula (HHFNC) and noninvasive positive pressure ventilation (NPPV) in patients with chronic obstructive pulmonary disease (COPD) complicated with type 2 respiratory failure after extubation. Methods Seventy-two patients with COPD complicated with type 2 respiratory failure were enrolled after extubation and were randomized into HHFNC group and NPPV group at 1:1 ratio, with 36 patients in each group. The blood gas analysis index, respiratory rate, heart rate, mean arterial pressure, reintubation rate, incidence of tracheotomy, intensive care unit stay, incidence of adverse events and mortality were compared between the two groups before treatment and 2, 12, 24 h after treatment. Results The pH at 24 h, partial pressure of oxygen in artery (PaO₂) at 2 h and 12 h, and oxygenation index (PaO₂/FiO₂) at 2 h and 12 h after treatment were significantly higher in the HHFNC group compared with the NPPV group (all P<0.05), while partial pressure of carbon dioxide in artery (PaCO2) at 12 h, respiratory rate at 2 h, 12 h and 24 h, and heart rate at 12 h and 24 h after treatment were significantly lower in the HHFNC group compared with the NPPV group (all P<0.05). There were no significant differences in reintubation rate, incidence of tracheotomy or intensive care unit stay between the two groups (all P>0.05), while the overall incidence of adverse events, intolerance rate, flatulence rate and aspiration rate were significantly lower in the HHFNC group than those in the NPPV group (all P<0.05). The mortality rates were not significantly different between the two groups (P>0.05). Conclusion The short-time efficacy and safety of HHFNC are better than NPPV in treatment of COPD complicated with type 2 respiratory failure.