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Background: The goal of our study was to determine the impact of gastrointestinal bleeding (GIB) on in-hospital outcomes among acute respiratory distress syndrome (ARDS) patients, and subsequently determine the potential risk factors for the development of GIB. Methods: ARDS patients with and without GIB were identified using the National Inpatient Sample (2002 - 2012). Linear regression analysis was used to assess impact of GIB on in-hospital mortality, length of stay and total charges. Univariate logistic regression was used to determine associated odds ratios (OR) for causes of ARDS and common comorbid conditions. Results: We identified 149,190 ARDS patients. The incidence of GIB was the highest among patients > 60 years (P < 0.001). GIB was associated with longer hospitalization days (7.3 days versus 11.9 days, P < 0.001), higher mortality (11% versus 27%, P < 0.001) and greater economic burden ($82,812 versus $45,951, P < 0.001). GIB was common in cirrhosis (OR: 8.3), peptic ulcer disease (OR: 3.7), coagulopathy disorders (OR: 3.003), thrombocytopenia (OR: 2.6), anemia (OR: 2.5) and atrial fibrillation (OR: 1.5). ARDS secondary to aspiration pneumonia (OR: 2.0), pancreatitis (OR: 2.0), sepsis (OR: 1.6) and community acquired pneumonia (OR: 0.8) was more likely to have GIB. Conclusion: Our study demonstrates that GIB in ARDS patients is associated with significant increased mortality, hospitalization and health care cost. J Clin Med Res. 2019;11(1):42-48 doi: https://doi.org/10.14740/jocmr3660