Abstract： Background Early withdraw from invasive mechanical ventilation (MV) followed by noninvasive MV is a new strategy for changing modes of treatment. This study was conducted to estimate the feasibility and the efficacy of early extubation and sequential noninvasive MV commenced at beginning of pulmonary infection control window in patients with exacerbated hypercapnic respiratory failure caused by chronic obstructive pulmonary diseases (COPD). Methods A prospective, randomized controlled study was conducted in eleven teaching hospitals' respiratory or medical intensive care units in China. Ninety intubated COPD patients with severe hypercapnic respiratory failure triggered by pulmonary infection (pneumonia or purulent bronchitis) were involved in the study. When the pulmonary infection had been controlled by antibiotics and comprehensive therapy, the "pulmonary infection control window (PIC window)" has been reached. Each case was randomly assigned to study group (extubation and noninvasive MV via facial mask immediately) or control group (invasive MV was received continuously after PIC window by using conventional weaning technique).Results Study group (n=47) and control group (n=43) had similar clinical characteristics initially and at the time of PIC window. Compared with control group, study group had shorter duration of invasive MV ［(6.4±4.4) days vs (11.3±6.2) days, P=0.000］, lower rate of ventilator associated pneumonia (VAP) (3/47 vs 12/43, P=0.014), fewer days in ICU ［(12±8) days vs (16±11) days, P=0.047］ and lower hospital mortality (1/47 vs 7/43, P=0.025).Conclusions In COPD patients requiring intubation and invasive MV for hypercapnic respiratory failure, which is exacerbated by pulmonary infection, early extubation followed by noninvasive MV initiated at the start of PIC window may decrease significantly the duration of invasive MV, the risk of VAP and hospital mortality.