Background: The aim of this study was to evaluate the predictive value of cystatin C (CysC) and estimated glomerular filtration rate (eGFR) regarding vascular lesions and their severity in patients with acute coronary syndrome (ACS). Methods: According to the results of coronary angiography, 195 ACS patients were divided into a single-vascular-lesion group (91 cases), a dual-vascular-lesion group (67 cases), and a multiple-vascular-lesion group (37 cases) to assess the severity of coronary artery disease according to Gensini scores and to analyze the correlations of CysC and eGFR level with vascular lesions and severity in ACS patients. Results: Intergroup comparisons of univariate and multivariate regression analyses showed that CysC was positively correlated with vascular lesions (P < 0.05), but eGFR showed no correlation. Regarding the severity of vascular lesions, CysC was positively correlated with Gensini score (Pearson's correlation coefficient r = 0.1811, P < 0.05), but eGFR was not correlated (P > 0.05). Conclusions: Serum CysC levels could reflect the severity of vascular lesions in ACS patients, and a high CysC level had predictive value regarding the severity of vascular lesions in ACS.