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Background: Cangrelor, an intravenous P2Y12-receptor inhibitor, is a reversible and short-acting antithrombotic medication non-inferior to irreversible glycoprotein IIb/IIIa inhibitors (GPIs) like eptifibatide. There are insufficient data to compare the medications in endovascular thrombectomies (EVTs) requiring emergent platelet inhibition., Objective: To review our institution's experience with cangrelor in EVT and compares its safety and efficacy against GPIs., Methods: A large healthcare system retrospective review identified all patients who had received cangrelor or eptifibatide intraoperatively during EVT between December 2018 and March 2023 for this cohort study. Clinical data were reviewed. Functional status was defined by the modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) at multiple time points. Multivariate regression was performed., Results: Of 1010 EVT patients, 36 cangrelor and 104 eptifibatide patients were selected. There were no differences in baseline function or presentations. Cangrelor was frequently administered for stenting tandem occlusions (n=16, 44.4%), and successful reperfusion occurred in 30 (83.3%) patients. On multivariate analysis, cangrelor was associated with decreased odds of hemorrhagic conversion (adjusted OR (aOR)=0.76, P=0.004) and symptomatic hemorrhage (aOR=0.86, P=0.021). There were no differences in thrombotic re-occlusion. Cangrelor was associated with a lower 24-hour NIHSS score (7.0 vs 12.0, P=0.013) and discharge NIHSS score (3.0 vs 9.0, P=0.004). There were no differences in in-hospital mortality or length of stay. Cangrelor was associated with improved odds of favorable outcome, defined as mRS score 0-2, at discharge (aOR=2.69, P=0.001) and on 90-day follow-up (aOR=2.23, P=0.031)., Conclusion: Cangrelor was associated with a decreased risk of hemorrhagic conversion and might lead to favorable functional outcomes for patients during hospitalization in comparison with GPIs. Prospective studies are warranted to investigate its use in EVT., Competing Interests: Competing interests: Disclosures: JTF and JM are members of the Society of Neurointerventional Surgery Board of Directors., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)