Background Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared with clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, data regarding PR from ticagrelor and the outcomes are lacking. Methods This study aimed to determine the association between PR after a ticagrelor loading dose (LD), assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention. The authors performed a prospective, multicenter observational study on patients treated with percutaneous coronary intervention for ACS. The VASP index was used to assess PR after ticagrelor LD. The primary endpoint was the link between major adverse cardiac events (MACE) and PR. Results Among the included 530 patients with ACS, 185 (34.5%) were admitted for ST-segment elevation myocardial infarction. This study observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1 ± 16.6%). At 1 month, 21 MACE (3.8%) and 29 Academic Research Consortium ≥2 bleeding events (5.5%) were recorded. Neither MACE nor bleeding were associated with PR (p = 0.34 and p = 0.78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (p = 0.03). PR was the only factor associated with acute definite stent thrombosis. Conclusion In patients receiving a ticagrelor LD while undergoing percutaneous coronary intervention for ACS, PR using the VASP does not predict MACE or bleeding at 1 month, but it is significantly associated with the occurrence of definite acute ST.