Objective: Of all spontaneous bleeding complications in patients with acute ST-elevation myocardial infarction (STEMI), upper gastrointestinal bleeding (UGIB) is the most common and of specific interest, because it can be prevented by several prophylactic measures. The purpose of this study was to investigate the in-hospital incidence, associated outcomes, and predictors of UGIB after STEMI. Methods: In this retrospective study, we analyzed the records of 2 791 patients with acute STEMI admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University between January 2018 and January 2022. The patients were divided into the UGIB group (n=61) and non-UGIB group (n=2 730) according to the presence or absence of upper gastrointestinal hemorrhage, respectively. Baseline clinical conditions, coronary lesions, in-hospital deaths, and in-hospital adverse events were compared between the two groups. Logistic regression analysis was also performed for risk factors that could lead to UGIB. Results: The in-hospital incidence of UGIB after STEMI was 2.2% (61/2 791). Hospital stay was significantly longer in the UGIB group [8(6, 12) days vs. 5 (4, 7) days, Z=3.28, P<0.001] and in-hospital mortality was significantly higher in the UGIB group than in the non-UGIB group (9.8% vs. 0.8%, χ2=0.63, P=0.001). Patients with UGIB were significantly older than those without UGIB (63±11 years vs. 58±11 years, t=-3.75, P<0.001). The serum creatinine level of UGIB patients was significantly higher than that of non-UGIB patients [(80(62, 98) mmol/L vs. 73(64, 84) mmol/L, Z=1.68, P=0.007], the red blood cell count of UGIB patients was significantly lower than that of non-UGIB patients [4.1(3.8, 4.6)×1012/L vs. 4.6(4.2, 4.9)×1012/L, Z=2.61,P<0.001], and the hemoglobin concentration of UGIB patients was significantly lower than that of non-UGIB patients [129(109, 141) g/L vs. 141(130, 152) g/L, Z=2.52,P<0.001]. Brain natriuretic peptide levels were significantly higher in UGIB patients than in non-UGIB patients [331(165, 644) ng/L vs. 181(89, 333) ng/L, Z=2.42,P<0.001]. Logistic regression analysis showed that age (OR=1.045, 95%CI 1.009-1.082, P=0.013); hemoglobin (OR=1.594, 95%CI 1.150-2.210, P=0.005); hematocrit (OR=0.181, 95%CI 0.060-0.546, P=0.002); and mean hemoglobin concentration (OR=0.845, 95%CI 0.752-0.951, P=0.005) were independent risk factors for UGIB in patients with STEMI. Logistic regression analysis of risk factors for in-hospital death revealed that concurrent UGIB was an independent risk factor for in-hospital death in patients with STEMI (OR=2.954, 95%CI 0.635-13.751, P=0.024). Conclusions: The incidence of in-hospital UGIB in STEMI patients was 2.2%, and the in-hospital mortality rate of STEMI complicated with UGIB increased to 9.8%. Concurrent UGIB was an independent risk factor for in-hospital death in patients with STEMI. The most important predictors of in-hospital UGIB in patients with STEMI were age, hemoglobin, hematocrit, and mean hemoglobin concentration.