Objective To study the effect of different proton pump inhibitors (PPIs) on the prevention of gastrointestinal hemorrhage and the influence to platelet aggravation rate (PAR) and cardiovascular events in elderly patients treated with clopidogrel+aspirin after percutaneous coronary intervention (PCI). Methods A total of 280 patients taking clopidogrel+aspirin after PCI were randomly divided into 5 groups, including group A (control): basic treatment (aspirin+clopidogrel), group B: basic treatment with omeprazole 20mg bid, group C: basic treatment with rabeprazole 10mg bid, group D: basic treatment with lansoprazole 30mg qd, group E: basic treatment with esomeprazole 20mg bid. Patients were observed for 12 months after the treatment. Patients who presented with gastrointestinal damage (hematemesis, abdominal discomfort, bellyache) received gastroscopic examination. Adverse cardiovascular events and PAR were also determined. Results The incidence of gastrointestinal injury was 28.85%, 12.28%, 10.53%, 10.34% and 8.93% in group A, B, C, D and E respectively. There was significant difference between group A and other 4 groups (P＜0.05). The incidence of cardiovascular events was 5.77%, 14.04%, 7.02%, 8.62% and 8.93%, and PAR was 22%±7%, 34%±11%, 27%±6%, 26%±7%, and 23%±6% respectively. The incidence and PAR increased greatly in group B. Conclusion The gastrointestinal hemorrhage of patients treated with clopidogrel+aspirin can be prevented safely and effectively with PPIs. Omeprazole can promote PAR and thus decrease the antiplatelet effect so as to increase the occurrance of cardiovascular events, while other PPIs have no influence on antiplatelet effect.