To analyze the risk factors for upper gastrointestinal bleeding (UGIB) in patients with ST-segment elevation myocardial infarction (STEMI) during double antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). A total of 388 patients treated from January 2015 to September 2017 due to STEMI were selected. Thirty-two cases of UGIB occurring during DAPT after PCI were included as a UGIB group, and another 356 cases without UGIB were set as a control group. Age, gender, body mass index, smoking, drinking, history of previous diseases (hypertension, diabetes and digestive tract diseases), infection of Helicobacter pylori (Hp), combined use of other drugs (statins, NSAIDs, β receptor blockers, PPI, H2RA and dabigatran etexilate), as well as serum levels of creatinine (Cr), alanine transaminase (ALT) and C-reactive protein (CRP) were compared. The risk factors for UGIB were subjected to univariate and logistic regression analyses. Compared with the control group, the UGIB group had significantly longer hospital stay, and higher proportion of discontinuation of antithrombotic drugs and mortality rate (P<0.05). Logistic regression analysis showed that age (P=0.002), smoking (P=0.000), Hp infection (P=0.020), history of digestive tract diseases (P=0.030) and renal insufficiency (P=0.041) were independent risk factors for UGIB, and use of PPI (P=0.028) was a protective factor for UGIB. Old age, smoking, Hp infection, history of digestive tract diseases and renal insufficiency are risk factors for UGIB caused by PCI combined with DAPT in patients with STEMI. Proper use of PPI thereafter can reduce the incidence rate of UGIB.