BACKGROUND The risk of upper gastrointestinal bleeding (UGIB) is increased among end-stage renal disease (ESRD) patients compared to the general population. However, correlates of UGIB among ESRD patients remain unknown. We conducted a cohort study of dialysis patients to ascertain risk factors for UGIB. METHODS Data from the United States Renal Data System Dialysis Morbidity and Mortality Studies, Waves 2-4 were used to identify risk factors for incident UGIB among ESRD patients. First hospitalizations for UGIB were identified using hospital diagnosis codes between 12/31/93 and 12/31/99. Cox regression was used to estimate the association between predictors of interest and first diagnosis of UGIB. RESULTS Cases of UGIB (698) were observed over 30648 patient years of follow-up. Before adjustment for confounding factors, increasing age, diabetes, former and current smoking, cardiovascular disease (CVD), lower serum albumin, malnutrition, and inability to ambulate independently were associated with an increased risk of UGIB, while African Americans and transplant patients had a lower risk of UGIB. After adjustment, African American race was associated with a lower risk of UGIB (RR = 0.90; 0.82, 0.98), while current smoking (RR = 1.11; confidence interval 1.03, 1.19), history of CVD (RR = 1.32; 1.10, 1.59), and inability to ambulate independently (RR = 1.32; 1.07, 1.63) were associated with a higher risk of UGIB. Age, gender, diabetes, lower serum albumin, nourishment, treatment modality, aspirin use, nonsteroidal anti-inflammatory drug (NSAID) use, and antiplatelet or anticoagulant medication use were not found to be significantly related to the risk of UGIB after adjustment for potential confounding factors. CONCLUSIONS CVD, current smoking, and risk factors suggesting more disability are associated with a greater risk of UGIB among patients with ESRD.