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Background To develop appropriate management strategies for patients who take low-dose aspirin, it is important to identify the risk factors for GI injury. However, few studies have described the risk factors for small-bowel injury in these patients. Objective To investigate factors influencing the risk of small-bowel mucosal breaks in individuals taking continuous low-dose aspirin. Design Capsule endoscopy data were collected prospectively from 5 institutions. Setting Yokohama City University Hospital and 4 other hospitals. Patients A total of 205 patients receiving treatment with low-dose aspirin for over 3 months. Interventions Colonoscopic and upper GI endoscopy had been performed in all of the patients before the capsule endoscope evaluation. Main Outcome Measurements Risk factors for small-bowel mucosal breaks. Results Of the 198 patients (141 male; mean age 71.9 years) included in the final analysis, 114 (57.6%) had at least 1 mucosal break. Multivariate analysis identified protein pump inhibitor (PPI) use (OR 2.04; 95% confidence interval [CI], 1.05-3.97) and use of enteric-coated aspirin (OR 4.05; 95% CI, 1.49-11.0) as independent risk factors for the presence of mucosal breaks. Limitations Cross-sectional study. Conclusion PPI use appears to increase the risk of small-bowel injury in patients who take continuous low-dose aspirin. Clinicians should be aware of this effect of PPIs; new strategies are needed to treat aspirin-induced gastroenteropathy.