Objective: To investigate the effects of invasive-noninvasive mechanical ventilation sequential therapy in treatment of chronic obstructive pulmonary disease (COPD) combined with respiratory failure. Methods: 88 COPD combined respiratory failure patients were divided into 2 groups according to the patients' wishes. The patients in control group (n=44) were given invasive mechanical ventilation, while the patients in observation group (n=44) were given invasive-noninvasive mechanical ventilation sequential therapy. The treatment-related indicators, blood gas analysis indexes, pulmonary function indexes and adverse events of patients in 2 groups were compared. Results: After treatment, the invasive ventilation time, total mechanical ventilation time, hospital stays of patients in observation group were obviously shorter than control group (P<0.05); PaO ₂, FVC, FEV1 were obviously higher than control group (P<0.05); PaCO ₂, and the incidence of weaning failure rate and VAP were obviously lower than control group (P<0.05). Conclusions: Invasive-noninvasive mechanical ventilation sequential therapy can shorten the mechanical ventilation time of COPD combined respiratory failure patients, improve pulmonary function and gas analysis indexes, reduce the incidence of adverse events, and is safe and reliable .