Objective: To investigate the preventive effect of pantoprazole on gastrointestinal injury induced by dual antiplatelet drugs after percutaneous coronary intervention (PCI). Methods: The data of 142 patients with coronary heart disease who received PCI Treatment in our hospital from May 2016 to August 2019 and were followed up for more than 12 months were retrospectively analyzed. According to whether or not pantoprazole was used after PCI, they were divided into a conventional group (aspirin + clopidogrel) of 68 cases and a study group (aspirin + clopidogrel + pantoprazole) of 74 cases. The antiplatelet effect, gastrointestinal injury events and cardiovascular adverse events were compared between the 2 groups, and the influencing factors of gastrointestinal injury were analyzed. Results: There was no significant difference in platelet aggregation rate and incidence of cardiovascular events between the 2 groups (P>0.05). The incidence of digestive tract injury in the study group 12 months after PCI was lower than that in the conventional group (P<0.05). The risk factors of gastrointestinal injury after PCI were smoking history, peptic ulcer history and renal insufficiency. Pantoprazole was the protective factor (OR=0.382, 95%CI: 0.134–0.768, P<0.05). Conclusion: Pantoprazole combined with dual antiplatelet drugs after PCI can effectively prevent gastrointestinal injury, and does not affect the antiplatelet effect and increase the risk of cardiovascular events.