Background: Patients with upper gastrointestinal bleeding (UGIB) often require urgent or emergent esophagogastroduodenoscopy (EGD) and are at risk of complications such as aspiration of gastric content or blood. The role of prophylactic endotracheal intubation (PEI) in the absence of usual respiratory status-related indications is not well established. Methods: We searched Medline, EMBASE, Cochrane Library's Central Register of Controlled Trials (CENTRAL) and SCOPUS from inception through July 2017 without date or language of publication restriction. We included studies that compared PEI with usual care (UC) in patients with acute UGIB, and reported any of the following outcomes: aspiration, pneumonia, mortality and length of stay. We excluded studies in which majority of included patients required intubation due to respiratory failure or decreased level of consciousness. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence for each outcome. Results: We did not identify any randomized trials on this topic. We included 10 observational studies (n = 6068). We were not able to perform any adjusted analyses. PEI was associated with a significant increase in aspiration (OR 3.85, 95% CI, 1.46, 10.25; P = 0.01; I2 = 56%; low-quality evidence), pneumonia (OR 4.17, 95% CI, 1.82, 9.57; P = 0.0007; I2 =52%; low-quality evidence) and hospital length of stay (mean difference 0.86 days, 95% CI 0.13, 1.59; P = 0.02; I2 = 0; low-quality evidence), without clear effect on mortality (OR 1.92, 95% CI, 0.71, 5.23; P = 0.2; I2 = 95%; very low-quality evidence). Conclusions: Low- to very low-quality evidence from observational studies suggests that PEI in the setting of UGIB may be associated with higher rates of respiratory complications and, less likely, with increased mortality. Although the results are alarming, the lack of higher quality evidence calls for randomized trials to inform practice.