BACKGROUND: Patients with COPD are at a high risk for pulmonary embolism (PE) because of systemic inflammation and co-existing comorbidities. We aimed to determine the incidence, risk factors, and impact of PE during COPD exacerbation requiring mechanical ventilation. METHODS: This prospective cohort study was conducted between March 2013 and May 2017. Subjects with severe COPD exacerbation requiring mechanical ventilation were included. A lower-limb ultrasonography or a multidetector helical computed tomography scan (MDCT) was performed according to Wells score. Subjects with ultrasonographic signs of phlebitis underwent MDCT to confirm PE. RESULTS: During the study period, 131 COPD subjects were admitted to the ICU for severe COPD exacerbation. The incidence of PE was 13.7%. Factors independently associated with PE were increased sputum volume (odds ratio [OR] ؍ 0.106, 95% CI 0.029-0.385, P ؍ .001), recent immobilization > 7 d (OR ؍ 5.024, 95% CI 1.470-17.170, P ؍ .01), age > 70 y (OR ؍ 5.483, 95% CI 1.269-23.688, P ؍ .02), and invasive mechanical ventilation at ICU admission (OR ؍ 3.615, 95% CI 1.005-13.007, P ؍ .049). ICU mortality was higher in the PE group (44% vs 11%). Predictive factors of mortality were PE (OR ؍ 7.135, 95% CI 2.042-24.931, P ؍ .002), SAPS II score at admission OR ؍ 1.040, 95% CI 1.005-1.077, P ؍ .02), and duration of mechanical ventilation (OR ؍ 1.098, 95% CI 1.044-1.154, P < .001). CONCLUSION: PE was found to be a common etiology of severe exacerbation of COPD, leading to high mortality. Age, invasive mechanical ventilation, and immobilization were risk factors for PE.