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 event (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/Conclusion 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.