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Introduction: Potential benefit with potent platelet inhibition in patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI) has been discussed. The aim of this study was to compare a potent P2Y12 inhibition strategy using ticagrelor with clopidogrel in CCS patients referred for coronary angiography (CA) and PCI if feasible. Methods: In this retrospective real-world study, patients referred for outpatient CA due to suspected CCS were included. To adjust for group differences, a propensity score reflecting the probability of being treated with ticagrelor was calculated and added to the logistic regression outcome model. Results: In total, 1,003 patients were included in the primary analysis (577 treated with clopidogrel and 426 with ticagrelor). Among clopidogrel-treated patients, 132 (22.9%) experienced a bleeding complication compared with 93 (21.8%) among ticagrelor-treated patients, with no significant difference between the groups (p = 0.70). There was no difference in bleeding severity. Furthermore, we observed no statistically significant difference in major adverse cardiovascular events (MACE [death, stent thrombosis, myocardial infarction, or stroke]) (1.2% vs. 2.3%, p = 0.17). A subgroup analysis restricted to patients undergoing PCI ad hoc displayed a similar pattern. Also, patients undergoing CA without PCI ad hoc frequently experienced a bleeding complication, with no difference between the two treatments (21.0% vs. 17.3%, p = 0.27). Propensity score adjusted analyses confirmed the results. Discussion: In patients with CCS referred for CA and PCI if feasible, a more potent P2Y12 inhibition strategy with ticagrelor was not associated with bleeding complications or MACE compared with clopidogrel. [ABSTRACT FROM AUTHOR]