Background Gastrointestinal bleeding (GIB) has been reported to be more common in patients with chronic renal failure and end-stage renal disease requiring hemodialysis with higher mortality than in the general population. Limited epidemiological data exist on the annual number of hospitalizations, demographic variation, cost of care, and outcomes for GIB in patients with acute kidney injury (AKI) requiring and not requiring hemodialysis (HD). The main objective of this study was to analyze the trends of GIB in patients with AKI requiring HD and those not requiring HD during hospitalization. Methods and Results We analyzed the National (Nationwide) Inpatient Sample (NIS) database for all subjects with a discharge diagnosis of AKI as the primary or secondary diagnosis during the period from 2001 to 2011. Subjects with a discharge diagnosis of hemodialysis and GIB were then identified from the pool and trends were analyzed. A significant rise in the annual number of hospitalizations with AKI was found with a greater proportion being discharged without HD. From 2001 to 2011, there were 19,393,811 hospitalizations with a discharge diagnosis of AKI of which 1,424,692 (7.3%) received HD (HD group), whereas 17,969,119 (92.7%) did not receive HD (non-HD group) (p < 0.0001). The male gender was more commonly affected by GIB than the female gender in both groups (p < 0.0001). The cost of care per hospitalization for GIB patients in the HD group increased over the study period with average found to be $61,463 (adjusted for inflation, p < 0.0001), whereas for GIB patients in the non-HD group, it showed a slight decrease in trend with the average found to be $28,419 (p < 0.0001). All-cause mortality was higher for GIB patients in the HD group (38.1%) than in the non-HD group (25.1%) (p < 0.0001). Conclusions GIB is more common and associated with higher all-cause inpatient mortality in patients receiving HD in comparison to non-HD patients.