BACKGROUND The aim of this study was to systematically evaluate the effect of oral Xa inhibitors plus antiplatelet therapy in the treatment of coronary artery disease. MATERIAL AND METHODS All randomized controlled trials (RCTs) about antiplatelet therapy plus Xa factor inhibitors for coronary artery disease from database inception to January 2019 were searched for and collected from PubMed, Embase, and the Cochrane Library. Two reviewers extracted and analyzed the data independently. Additionally, RevMan 5.0 software was applied for meta-analysis. RESULTS Seven RCTs with 50 044 patients were included. The meta-analysis results showed that treatment with antiplatelet therapy plus Xa factor inhibitors in patients with coronary artery disease could significantly reduce the risk of ischemic events (P<0.00001). Besides, risk of all-cause mortality (P=0.003), myocardial infarction (P=0.02) and ischemic stroke (P<0.0001) were also significantly reduced. However, risk of massive hemorrhage after TIMI (P<0.00001), minor hemorrhage after TIMI (P<0.00001), and intracranial hemorrhage (P=0.006) were significantly increased, respectively. Xa inhibition drugs also intended to increase risk of fatal bleeding, but there was no significant difference (P=0.08). CONCLUSIONS Antiplatelet therapy plus Xa factor inhibitors in patients with coronary artery disease was effective, which could reduce the risk of ischemic composite endpoints, all-cause mortality, myocardial infarction, and ischemic stroke. However, it could significantly increase risk of bleeding in terms of safety.