Background Unplanned 30-day readmissions have a negative impact on patients and healthcare systems. Mechanically ventilated ED patients are at high risk for complications, but factors associated with readmission are unknown. Objective (1) Determine the rate of 30-day hospital readmission for ED patients receiving mechanical ventilation. (2) Identify associations between ED-based risk factors and readmission. Design Retrospective cohort study. Setting Tertiary-care, academic medical centre. Patients Adult ED patients receiving mechanical ventilation. Measurements Baseline demographics, comorbid conditions, illness severity and treatment variables were collected, as were clinical outcomes occurring during the index hospitalisation. The primary outcome was 30-day hospital readmission rate. Multivariable logistic regression was used to evaluate factors associated with the primary outcome. Results A total of 1262 patients were studied. The primary outcome occurred in 287 (22.7%) patients. There was no association between care in the ED and readmission. During the index hospitalisation, readmitted patients had shorter ventilator, hospital and intensive care unit duration (P<0.05 for all). The primary outcome was associated with African-American race (adjusted OR 1.34 (95% CI 1.02 to 1.78)), chronic obstructive pulmonary disease (adjusted OR 1.52 (95% CI 1.12 to 2.06)), diabetes mellitus (adjusted OR 1.34 (95% CI 1.02 to 1.78)) and higher illness severity (adjusted OR 1.03 (95% CI 1.01 to 1.05)). Conclusions Almost one in four mechanically ventilated ED patients are readmitted within 30 days, and readmission is associated with patient-level and institutional-level factors. Strategies must be developed to identify, treat and coordinate care for the most at-risk patients.