Background and Objective: Over half of all patients admitted with acute ischemic stroke (AIS) suffer gastrointestinal complications. Our goal was to determine the burden of gastrointestinal bleeding (GIB) in hospitalized patients with AIS using the largest, all-payer, inpatient database in the United States. Methods: The Nationwide Inpatient Sample (2002-2011) was queried to identify all adult patients with a primary diagnosis of AIS with and without a secondary diagnosis of GIB. We used multivariable analyses, adjusting for pertinent confounders, to identify risk factors for GIB in AIS patients and to determine the effect of GIB on in-hospital complications and outcomes. Results: Of 3,988,667 patients hospitalized for AIS, there were 49,348 cases of GIB (1.24%). In multivariable analysis, patients with a history of peptic ulcer disease (odds ratio [OR]: 2.45, 95% confidence interval [CI]: 2.10-2.86) and liver disease (OR: 2.42, 95% CI: 2.26-2.59) were more likely to suffer GIB. Patients suffering from GIB were more likely to require intubation (OR: 2.04, 95% CI: 1.95-2.13) and blood transfusion (OR: 11.31, 95% CI: 11.00-11.63). The occurrence of GIB increased hospital length of stay by an average of 5.8 days and total costs by $14,120 per patient (all P<.0001). GIB was independently associated with a 46% increased likelihood of severe disability and 82% increased likelihood of in-hospital death (all P<.0001). Conclusions: GIB occurrence in patients with AIS is relatively rare but is associated with poor in-hospital outcomes, including mortality. We identified risk factors associated with GIB in AIS, which allows physicians to monitor patient populations at the highest risk. (C) 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.