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Background: COVID-19 vaccination has been associated with reduced risk of acute coronary syndrome (ACS); however, several studies have reported cardiovascular complications following vaccination. We aimed to investigate the effect of COVID-19 vaccination status on the treatment and outcome of ACS patients., Methods: The study was based on the 2021 Acute Coronary Syndrome Israeli Survey. Patients were stratified into two groups according to COVID-19 vaccination status, vaccinated compared to unvaccinated. Patients who had received at least 2 vaccination doses up to 1 week prior to ACS hospitalization were considered vaccinated. The primary endpoint was 1-year all-cause mortality., Results: A total of 1261 patients with ACS were included, of whom 990 (78.5%) were vaccinated. Vaccinated patients were older and less frequently smokers. There were no significant differences in coronary reperfusion rates and treatment with guideline-based medical therapy during hospital stay and at discharge. The primary endpoint of 1-year all-cause mortality occurred in 38 (3.8%) and 14 (5.2%) patients in the vaccinated and unvaccinated groups respectively (P = 0.42). 30-day MACE occurred in 94 (9.5%) in the vaccinated patients compared to 31 (11.5%) in the unvaccinated group (P = 0.39). These results remained similar following adjustment for confounders., Conclusion: There was no association between COVID-19 vaccination status and the outcomes of patients with ACS. Our findings provide support for the cardiovascular safety of COVID-19 mRNA vaccines in patients at high cardiovascular risk., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)