Knowledge on the risk of gastrointestinal (GI) bleeding in hemodialysis patients is limited. We evaluated the risk of GI bleeding in hemodialysis patients compared with non-hemodialysis patients. We performed a retrospective cohort study from 1996 to 2017 at the Graduate School of Medicine, University of Tokyo, and Horinouchi Hospital. We analyzed patients on hemodialysis for chronic renal failure and controls not on hemodialysis. The primary endpoint was GI bleeding. A survival analysis was performed to estimate the cumulative incidence and hazard ratio of GI bleeding. A total of 14451 patients were analyzed (417 hemodialysis and 14034 non-hemodialysis patients). In total, 524 GI bleeding events occurred. Upper and lower GI bleeding occurred in 432 and 92 patients in the hemodialysis and non-hemodialysis groups, respectively. The most frequent source of upper and lower GI bleeding was gastric ulcer and colonic diverticular bleeding, respectively. The cumulative incidence of GI bleeding was 4.44% at 1year, 7.15% at 3years, and 10.40% at 5years in hemodialysis patients; the respective rates were 2.35%, 2.98%, and 3.79% in non-hemodialysis patients during a mean follow-up period of 3.5years. Hemodialysis was significantly associated with an increased risk of GI bleeding after adjustment (hazard ratio 1.67, P=0.01, 95% confidence interval 1.13-2.50). Hemodialysis patients had a GI bleeding rate of 10% over 5years, and hemodialysis was a risk factor for GI bleeding.