Objective: To explore the timing of treatment of invasive mechanical ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) combined with severe respiratory failure, and to analyze the prognostic influencing factors. Methods: 161 patients with AECOPD combined with severe respiratory failure who were treated in Beijing Shijitan Hospital Affiliated to Capital Medical University from March 2020 to December 2021 were selected, they were divided into early group (n = 89) and delayed group (n = 72) according to the time of endotracheal intubation, the clinical indicators, blood gas analysis indicators and mortality (prognosis) within 28 d were compared after treatment between the two groups. Patients were divided into death group (n = 29) and survival group (n = 132) according to different prognosis, the general and laboratory data of patients were collected, univariate and multivariate Logistic regression were used to analyze the influencing factors on the prognosis of patients with AECOPD combined with severe respiratory failure. Results: The invasive ventilation time, total mechanical ventilation time, and intensive care unit (ICU) hospitalization time in the early group were shorter than those in the delayed group (P < 0.05) The arterial partial pressure of carbon dioxide (PaCO2) in two groups decreased after treatment compared with before treatment, the oxygenation index (OI), and arterial partial pressure of oxygen (PaO2) were higher than that before treatment, and the degree of change in the early group was greater than that in the delayed group (P < 0.05) The mortality rate within 28 d in the delayed group was 15/72 (20.83%). The mortality rate within 28 d in the early group was 14/89 (15.73%), there was no difference in 28 d mortality rate of patients between the two groups (P>0.05). The results of the univariate analysis showed that influencing factors on the prognosis of patients with AECOPD combined with severe respiratory failure were concurrent ventilator-associated pneumonia, concurrent multiple organ insufficiency syndrome, age, PaCO2, hemoglobin(HB), blood urea nitrogen (BUN), white blood cell count (WBC), pH value, neutrophil count / lymphocyte count ratio (NLR), platelet count / lymphocyte count (PLR), C-reactive protein (CRP), D-Dimer (D-D), and B-type natriuretic peptide was associated (P<0.05). The results of multivariate Logistic regression analysis showed that concurrent ventilator-associated pneumonia, concurrent multiple organ insufficiency syndrome, higher PaCO2, older age, lower Hb, lower pH value and higher D-D were risk factors for poor prognosis in patients with AECOPD combined with severe respiratory failure (P<0.05). Conclusion: Early use of invasive mechanical ventilation in patients with AECOPD combined with severe respiratory failure, it can effectively improve blood gas analysis, reduce invasive ventilation time, total mechanical ventilation time, ICU hospitalization time. Concurrent ventilator-associated pneumonia, concurrent multiple organ insufficiency syndrome, higher PaCO2, older age, lower Hb, lower pH value and higher D-D both are leading to risk factors for poor prognosis in patients with AECOPD combined with severe respiratory failure. [ABSTRACT FROM AUTHOR]