Background: The test characteristics of blood urea concentration in the identification of upper gastrointestinal bleeding (UGIB) or high-risk endoscopic lesions have not been clearly determined. This study aimed to elucidate if urea independently correlates with the presence of positive endoscopic findings in cases of presumed UGIB and understand the diagnostic value of this parameter when assessing a patient with potential UGIB. Methods: A retrospective cohort study was conducted at Hamilton Health Sciences hospitals examining patients who had upper endoscopy for presumed UGIB. Contingency tables were generated to determine the test characteristics of urea at different thresholds for prediction of UGIB. A crude OR was calculated for odds of bleeding being identified on endoscopy based on varying thresholds of urea, and adjusted ORs were calculated using logistic regression modelling. Results: Variables significantly associated with detecting a source of GI bleeding at endoscopy included increase in urea (OR 1.06, 95% CI 1.01–1.09), male gender (OR 2.02, 95% CI 1.08–3.77), presence of melena (OR 2.37, 95% CI 1.06–5.33), and hematemesis (OR 3.88, 95% CI 1.70–8.83), when adjusted for other covariates. The odds of identifying UGIB at endoscopy in patients with urea ≥10 mmol/L was 3.73 (95% CI 1.90–7.31) times higher than for patients with urea <10 mmol/L. Conclusion: Urea level is an independent predictor of positive endoscopic findings in presumed UGIB, and urea ≥10 mmol/L may be a useful threshold to help guide clinicians towards clinically significant bleeding that could warrant early endoscopic evaluation.