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Objectives: The outbreak of coronavirus disease 2019 is becoming a worldwide pandemic. Mechanical ventilation is lifesaving for respiratory distress, this study was designed to delineate the clinical features of the coronavirus disease 2019 patients with mechanical ventilation from a national cohort in China. Design: Prospective observational study. Setting: The rapid spread of severe acute respiratory syndrome coronavirus 2 has infected more than 7.7 million people and caused more than 423,000 deaths. Patients: Adult hospitalized coronavirus disease 2019 patients with mechanical ventilation from 557 hospitals from China. Interventions: None. Measurements and Main Results: From a nationwide cohort, 141 coronavirus disease 2019 cases with mechanical ventilation were extracted from 1,590 cases. Cigarette smoke, advanced age, coexisting chronic illness, elevated systolic blood pressure, high body temperature, and abnormal laboratory findings are common in these ventilated cases. Multivariate regression analysis showed that higher odds of in-hospital death was associated with invasive mechanical ventilation requirement (hazard ratio: 2.95; 95% CI, 1.40-6.23; p = 0.005), and coexisting chronic obstructive pulmonary disease (hazard ratio, 4.57; 95% CI, 1.65-12.69; p = 0.004) and chronic renal disease (hazard ratio, 5.45; 95% CI, 1.85-16.12; p = 0.002). Compared with patients with noninvasive mechanical ventilation, patients who needs invasive mechanical ventilation showed higher rate of elevated d-dimer (> 1.5 mg/L) at admission (hazard ratio, 3.28, 95% CI, 1.07-10.10; p = 0.039). Conclusions:The potential risk factors of elevated d-dimer level could help clinicians to identify invasive mechanical ventilation requirement at an early stage, and coexisting chronic obstructive pulmonary disease or chronic renal disease are independent risk factors associated with fatal outcome in coronavirus disease 2019 patients with mechanical ventilation. (Crit Care Med 2020; XX:00-00