Background: Nonvariceal upper gastrointestinal bleeding emerges as a major complication of using antiplatelet agents and/ or anticoagulants and represents a clinical challenge in patients undergoing these therapies.Aim: To characterize patients with nonvariceal upper gastrointestinal bleeding related to antithrombotics and their management, and to determine clinical predictors of adverse outcomes.Methods: Retrospective cohort of adults who underwent upper gastrointestinal endoscopy after nonvariceal upper gastrointestinal bleeding from 2010 to 2012. The outcomes were compared between patients exposed and not exposed to antithrombotics.Results: Five hundred and forty-eight patients with nonvariceal upper gastrointestinal bleeding (67% men; mean age 66.5 ± 16.4 years) were included, of which 43% received antithrombotics. Most patients had comorbidities. Peptic ulcer was the main diagnosis and endoscopic therapy was performed in 46% of cases. The 30-day mortality rate was 7.7% (n = 42), and 36% were bleeding-related. The recurrence rate was 9% and 14% of patients with initial endoscopic treatment needed endoscopic retreatment. There were no significant differences between the exposed and non-exposed groups in most outcomes. Co-morbidities, hemodynamic instability, high Rockall score, low hemoglobin (7.76 ± 2.72 g/dL) and higher international normalized ratio (1.63 ± 1.13) were associated significantly with mortality in a univariate analysis.Conclusions: Adverse outcomes were not associated with antithrombotic use. The management of nonvariceal upper gastrointestinal bleeding constitutes a challenge to clinical performance optimization and clinical cooperation.