Capsule endoscopy (CE) has shown that low-dose aspirin occasionally causes small bowel (SB) bleeding. We herein evaluated the protective effects of mucoprotective agents (MPAs) on SB bleeding in aspirin users using the nationwide database of claims data from the National Health Insurance Service (NHIS). As CE is an insured procedure, we constructed an aspirin-SB cohort using NHIS claims data, with a maximum follow- up period of 24 months. Patients with anemia, melena, or hematochezia that occurred within 4 weeks before and after performing CE were suspected to have SB bleeding. A Cox proportional hazards regression model was used to determine the risk factors for SB bleeding. Subgroup analyses were conducted among patients who used acid suppressants, such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists. A total of 15,542 aspirin users were included. Anticoagulant use (hazard ratio HR, 3.22), high Charlson comorbidity index score (≥ 2) (HR, 3.54), and PPI use (HR, 2.85) were significantly associated with SB bleeding, whereas eupatilin use (HR, 0.35) was a preventive factor. SB bleeding occurred more frequently in concurrent users of acid suppressants than in nonusers (1.3% vs. 0.5%). Subgroup analysis revealed that eupatilin significantly reduced the risk of SB bleeding in aspirin users with concurrent use of acid suppressants (HR, 0.23 vs. 2.55). Eupatilin was associated with a reduced risk of SB bleeding in both aspirin users and those with concomitant use of acid suppressants. Eupatilin use should be considered for aspirin users, especially for those concomitantly taking acid suppressants.