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Background: Dysphagia is common and independently predicts death in ICU patients. Risk factors for dysphagia are largely unknown, with sparse data available from mostly small cohorts without systematic dysphagia screening., Research Question: What are the key risk factors for dysphagia in ICU patients after invasive mechanical ventilation?, Study Design and Methods: Post hoc analysis of data from a monocentric prospective observational study (Dysphagia in Mechanically Ventilated ICU Patients [DYnAMICS]) using comprehensive statistical models to identify potential risk factors for postextubation dysphagia. A total of 933 primary admissions of adult medical-surgical ICU patients (median age, 65 years; interquartile range, 54-73; 666 [71%] men) were investigated in a tertiary care academic center. Patients received systematic bedside screening for dysphagia within 3 h postextubation. Dysphagia screening positivity (n = 116) was followed within 24 h by a confirmatory examination., Results: After adjustment for confounders, baseline neurologic disease (OR, 4.45; 95% CI, 2.74-7.24; P < .01), emergency admission (OR, 2.04; 95% CI, 1.15-3.59; P < .01), days on mechanical ventilation (OR, 1.19; 95% CI, 1.06-1.34; P < .01), days on renal replacement therapy (OR, 1.1; 95% CI, 1-1.23; P = .03), and disease severity (Acute Physiology and Chronic Health Evaluation II score within first 24 h; OR, 1.03; 95% CI, 0.99-1.07; P < .01) remained independent risk factors for dysphagia postextubation. Increased BMI reduced the risk for dysphagia (6% per step increase; OR, 0.94; 95% CI, 0.9-0.99; P = .03)., Interpretation: In ICU patients, baseline neurologic disease, emergency admission, and duration of invasive mechanical ventilation appeared as prominent independent risk factors for dysphagia. Because all ICU patients after mechanical ventilation should be considered at risk for dysphagia, systematic screening for dysphagia is recommended in respective critically ill patients., Trial Registry: ClinicalTrials.gov; No.: NCT02333201; URL: www.clinicaltrials.govclinicaltrials.gov., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)