Objective To estimate the feasibility and the efficacy of early extubation and sequential non-invasive mechanical ventilation (MV) in chronic obstructive pulmonary disease (COPD) with exacerbated hypercapnic respiratory failure.Methods Twenty-two intubated COPD patients with severe hypercapnic respiratory failure due to pulmonary infection (pneumonia or purulent bronchitis) were involved in the study. At the time of pulmonary infection control window (PIC window) appeared, when pulmonary infection had been significantly controlled (resolution of fever and decrease in purulent sputum, radiographic infiltrations, and leukocytosis) after the antibiotic and the comprehensive therapy, the early extubation was conducted and followed by non-invasive MV via facial mask immediately in 11 cases (study group). Other 11 COPD cases with similar clinical characteristics who continuously received invasive MV after PIC window were recruited as control group.Results All patients had similar clinical characteristics and gas exchange before treatment, as well as the initiating time and all indices at the time of the PIC window. For study group and control group, the duration of invasive MV was (7.1±2.9) vs (23.0±14.0) days, respectively, P