Purpose <p>Dual antiplatelet therapy (DAPT) is the cornerstone for patients with coronary atherosclerotic heart disease (CHD) undergoing percutaneous coronary intervention (PCI) while increasing the risk of bleeding, particularly when combined with gastrointestinal disease (GID). Rivaroxaban 10 mg once daily is widely used in Asia. This study compared the effects of low-dose rivaroxaban (10 mg daily) plus clopidogrel vs. DAPT in CHD patients with GID undergoing PCI.</p> Methods <p>In this prospective, single-center, randomized controlled trial, eligible CHD patients with GID undergoing PCI were randomized (1:1) to either the dual pathway inhibition (DPI) group (rivaroxaban 10 mg plus clopidogrel 75 mg daily) or the DAPT group (aspirin 100 mg plus clopidogrel 75 mg daily). The primary outcome was Bleeding Academic Research Consortium (BARC) type 2–5 bleeding. The secondary outcome was major adverse cardiovascular or cerebrovascular events (MACCE), which included cardiac death, nonfatal myocardial infarction, ischemia-driven target vessel revascularization, all-cause death, stent thrombosis, and stroke during the 6-month follow-up.</p> Results <p>A total of 1042 patients were enrolled and analyzed (DPI, 522; DAPT, 520). Low-dose rivaroxaban (10 mg daily) plus clopidogrel was non-inferior to DAPT in BARC type 2–5 bleeding [8 (1.5%) vs. 6 (1.2%), absolute risk difference 0.38%, 95% confidence interval (CI) (− 1.02–1.78), <i>p</i> &lt; 0.0001 for non-inferiority]. Abdominal pain was significantly lower in the DPI group (<i>p</i> = 0.009). Other abdominal discomforts, gastrointestinal bleeding, or MACCE were similar.</p> Conclusions <p>In CHD patients with GID undergoing PCI, low-dose rivaroxaban (10 mg daily) plus clopidogrel was non-inferior to DAPT.</p> Trial registration <p>Chinese Clinical Trial Registry ChiCTR2100044319. Registered on March 16, 2021.</p>