Objective: To describe the experience with upper gastrointestinal bleeding (UGIB) in two major Latin American hospitals, its main causes, treatment and prognosis, while exploring some risk factors associated with death. Design: Prospective cohort study. Patients and Methods: We included 464 patients older than 15 years of age from two reference centers. We studied some demographic variables, history, clinical presentation, treatment and mortality. We explored the association between those variables and death. Results: The mean age was 57.9 years, and the male: female ratio was 1.4:1. Three hundred and fifty-nine patients (77.4%) were seen for gastrointestinal bleeding (outpatient bleeding) and 105 patients (22.6%) were inpatients seen for UGIB. A total of 71.6% of patients admitted with the diagnosis of upper GI bleeding underwent upper GI endoscopy (EGD) within 24 hours. The main causes of bleeding were peptic ulcer (190 patients, 40.9%), erosive disease (162 patients, 34.9%) and variceal bleeding (47 patients, 10.1%). Forty-four patients died (9.5%). Patients who presented with bleeding due to other causes during hospitalization had a higher mortality risk than those whose complaints were related to gastrointestinal bleeding (RR 2.4, 95% CI 1.2-4.6). An increasing number of comorbidities, such as those described in the Rockall score, were also associated with a higher risk of mortality (RR 2.5, 95% CI 1.1-5.4). Conclusion: Intrahospital upper GI bleeding and the presence of comorbidities are risk factors for a fatal outcome. Identifying patients with a higher risk would help improve the management of patients with UGIB.