The efficacy and safety of ticagrelor and clopidogrel in patients with stable coronary artery disease (SCAD) undergoing percutaneous coronary intervention (PCI) remain uncertain. Thus, this study aimed to compare the efficacy and safety of ticagrelor and clopidogrel in patients with SCAD treated with PCI. A total of 9,379 patients with SCAD undergoing PCI who received dual antiplatelet therapy (DAPT) were consecutively enrolled in two groups, namely, ticagrelor (n=1,081) and clopidogrel (n=8,298) groups. Major adverse cardiovascular and cerebrovascular events (MACCEs) and bleeding events according to ticagrelor or clopidogrel use were compared. After propensity matching (n=1,081 in each group), ticagrelor was associated with fewer MACCEs compared with clopidogrel (3.6% vs. 5.7%, hazard ratio [HR]=0.62, 95% confidence interval [CI] 0.41-0.93, p=0.019), and the difference between ticagrelor and clopidogrel for bleeding events was nonsignificant (4.0% vs. 3.2%, HR=1.24, 95% CI 0.79-1.93, p=0.356). On the other hand, the difference between ticagrelor and clopidogrel for net adverse clinical events was significant (4.1% vs. 6.0%, HR=0.67, 95% CI 0.46-0.98, p=0.039). In a multivariate analysis, the use of ticagrelor, number of stents, previous history of diabetes, previous history of smoking, and ACC/AHA type B2 or C lesions were considered independent predictors of MACCEs, while radial artery access, previous history of stroke, and weight ＜60kg were independent predictors of bleeding events. Conclusions Ticagrelor was associated with a lower incidence of MACCEs without an increased risk of bleeding events in patients with SCAD receiving PCI.