OBJECTIVE： To investigate the effects of esomeprazole-based regimen on the related indicators of upper gastrointestinal bleeding in patients with long-term clopodogrel combined with aspirin treatment. METHODS： In the 96 patients long-term clopodogrel combined with aspirin treatment and upper gastrointestinal bleeding， 62 were helicobacter pylori positive by rapid urease test and the other 34 were helicobacter pylori negative （negative control group）. The 62 helicobacter pylori positive patients were divided into observation group （31 cases） and control group （31 cases） by random number table. Patients in negative control group and control group received Esomeprazole sodium for injection 40 mg during active bleeding， adding into 0.9％ Sodium chloride injection 100 ml， intravenous infusion， twice a day， stopping clopodogrel and aspirin at the same time； after 3 d of active bleeding stopped， Clopidogrel and Aspirin. Based on conventional， observation group was additionally given Esomeprazole magnesium enteric-coated tablet 20 mg， orally， twice a day+Amoxicillin capsule 1.0 g， orally， twice a day+Clarithromycin tablet， orally， twice a day， for 2 weeks. After 1 month， by 14C breath test. Eradication losers were given Esomeprazole magnesium enteric-coated tablet 20 mg in the second 2 month after treatment， orally， twice a day + Bismuth potassium citrate capsule 0.3 g， orally， twice a day + Amoxicillin capsule 1.0 g， orally， twice a day + Levofloxacin tablet 0.5 g， orally， once a day， for 2 weeks. All patients were followed-up for six months. Relief time of pain and gastrointestinal symptoms， and the rebleeding situation in all groups were observed， the eradiation situation and the incidence of adverse reactions in observation group were recorded. RESULTS： After treatment for the first time， 22 patients eradiated helicobacter pylori in observation group， with eradiation rate of 71.0％， the others were eradicated in the next treatment， the total eradiation rate was 100％. The incidence of upper gastrointestinal rebleeding in observation group was significantly lower than control group and negative control group， with statistical significance （P＜0.05）. And there were no significant differences in relief time of pain and gastrointestinal symptoms， and the incidence of adverse reactions （P＞0.05）. CONCLUSIONS： Esomeprazole-based regimen can reduce the incidence of upper gastrointestinal bleeding induced by long-term clopodogrel combined with aspirin treatment， with good safety.