Abstract: AIM:To evaluate the efficacy and safety of protecting the alimentary canal with pantoprazole when using the quadruple therapy: aspirin, clopidogrel, low molecular weight heparin (LMWH) and tirofiban hydrochloride in acute coronary syndrome (ACS). METHODS: Two hundred and ninety-six selected hospitalized patients with ACS were divided into observation group (n=184) and control group (n=112). Aspirin, clopidogrel, LMWH and 2-3 days of tirofiban were administered to all patients. On this basis, pantoprazole 40 mg i.v. was first administered by drip phleboclysis for 4-5 days and then changed to tablets (40 mg twice daily) for 8 days in the observation group. RESULTS: Occurrence of 8-day all-cause death, refractory angina pectoris, relapse myocardial infarction and emergency percutaneous coronary intervention (PCI) in the observation group was lower than that in the control group (P<0.05). The number of total hemorrhages, mild hemorrhages and midrange hemorrhages in the control group was higher than in the observation group (P<0.05). CONCLUSION: Intravenous injection and oral administration of pantoprazole decreased the 8-day rate of alimentary tract hemorrhage when using the quadruple anti-thrombosis therapy for ACS, thus decreasing the number of all-cause death for 8 days, intractable angina pectoris, intractable angina, relapse myocardial infarction and emergency PCI.