Background: The diagnostic yield of push enteroscopy (PE) in patients with unexplained overt GI bleeding is about 30%. The aim of this study was to assess for predictive factors of positive findings. Methods: A total of 182 patients referred to two endoscopic centers (European Georges Pompidou Hospital [Paris, France] and Erasmus Hospital [Brussels, Belgium]) for unexplained overt GI bleeding (melena [57%], hematochezia [26%], or hematochezia associated with melena [17%]) were included in this retrospective study. Predictive factors associated with positive findings at upper PE were studied by using uni-and multivariate analysis. Results: The overall diagnostic yield of upper PE was 34%(62/182), but lesions were found beyond the second duodenum in 25%of the patients (45/182). Factors significantly associated with positive findings at upper PE were the following. (1) In univariate analysis: the presence of melena, Hb level < 7 g/dL, blood transfusion >4 units per patient, chronic renal failure, disorder of hemostasis or effective anticoagulant treatment, history of intestinal arteriovenous malformation, and age > 65 years. (2) In multivariate analysis: chronic renal failure and presence of melena. If only jejunal lesions were considered, chronic renal failure was the only predictive factor associated with positive findings at upper PE in multivariate analysis. The severity of GI bleeding did not reach statistical significance (p = 0.06). Delay between GI bleeding and PE, number of previous standard endoscopies and previous episodes of bleeding were not associated with positive findings in upper PE. Conclusions: In patients with unexplained overt GI bleeding, upper PE has a higher diagnostic yield in patients with chronic renal failure and patients with melena (vs. hematochezia). Background: The diagnostic yield of push enteroscopy (PE) in patients with unexplained overt GI bleeding is about 30%. The aim of this study was to assess for predictive factors of positive findings. Methods: A total of 182 patients referred to two endoscopic centers (European Georges Pompidou Hospital [Paris, France] and Erasmus Hospital [Brussels, Belgium]) for unexplained overt GI bleeding (melena [57%], hematochezia [26%], or hematochezia associated with melena [17%]) were included in Predictive factors associated with positive findings at upper PE were studied by using uni-and multivariate analysis. Results: The overall diagnostic yield of upper PE was 34% (62/182), but lesions were found beyond the second duodenum in 25% of the patients (45/182). Factors significantly associated with positive findings at upper PE were the following. (1) In univariate analysis: the presence of melena, Hb level <7 g / dL, blood transfusion> 4 units per patient, chronic renal failure, disorder of hemostasis or effective anticoagulant treatment, history of intestinal arteriovenous malformation, and age> 65 years. (2) In multivariate analysis: chronic renal failure and presence of melena. If only jejunal lesions were considered, chronic renal failure was the only Predictive factor associated with positive findings at upper PE in multivariate analysis. The severity of GI bleeding did not reach statistical significance (p = 0.06). Delay between GI bleeding and PE, number of previous standard endoscopies and previous episodes of bleeding were not associated with positive findings in upper PE. Conclusions: In patients with unexplained overt GI bleeding, upper PE has a higher diagnostic yield in patients with chronic renal failure and patients with melena (vs. hematochezia).