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The presence of good coronary collateral circulation (CCC) can protect and preserve myocardium from ischemia, increase myocardial contractility, and reduce adverse clinical events. However, its impact on mortality is still a topic of debate, particularly in acute coronary syndrome (ACS). The aim of this study was to investigate the association of CCC with cardiac risk factors and in-hospital mortality in patients hospitalized with a diagnosis of ACS.The study population included 2286 patients with ACS who underwent coronary angiography and were found to have at least 90% significant lesion in at least one major coronary artery. The CCC was graded according to the Rentrop classification. The patients were classified into a poor CCC group (Rentrop grades 0−1, n=1859) or a good CCC group (Rentrop grades 2−3, n=427).Patients with good CCC had more high-risk patient characteristics such as older age, higher rate of Killip class of at least 2 at admission, lower left ventricular ejection fraction, and impaired renal functions compared with the patients with poor CCC. In multivariate analysis, the presence of good CCC [odds ratio (OR): 2.000; 95% confidence interval: 1.116–3.585; P=0.020], left ventricular ejection fraction less than 40% (OR: 2.381; P=0.003), Killip class of at least 2 at admission (OR: 3.609; P<0.001), age of at least 65 years (OR: 2.975; P=0.003), and hemoglobin (OR: 0.797; P=0.003) were independent predictors of in-hospital mortality.In contrast to previous studies, our study did not confirm a beneficial role of good CCC in patients with ACS; the presence of good CCC was even independently associated with increased in-hospital mortality in the multivariate analysis.