High sensitive C-reactive protein (hs-CRP) levels are associated with short- and long-term mortality in patients with acute coronary syndrome (ACS). We investigated whether baseline hs-CRP levels are associated with burden of coronary atherosclerosis assessed by SYNTAX score (SXScore).We enrolled 321 patients with ACS who underwent coronary angiography. The patients were divided into tertiles according to the SXScore: low SXScore (≤ 22), and intermediate-high SXScore (≥ 23).Subjects in the intermediate-high SXScore tertile had higher serum hs-CRP levels compare to low SXScore tertile patients (7.7 ± 3.4 mg/L versus 4.9 ± 2.5 mg/L, P < 0.001). The mean age of patients and prevalance of diabetes in the intermediate-high SXScore tertile were significantly higher than in the low SXScore tertile (63 ± 13 versus 58 ± 12 years P = 0.001 for age, P = 0.007 for diabetes). Multivariate logistic regression analysis showed that the strongest predictors of high SXScore were increased serum hs-CRP levels (OR: 1.14) together with multivessel disease (OR: 0.23), left ventricular ejection fraction (LVEF) (OR: 0.90), and troponin levels (OR: 1.12).Serum hs-CRP levels on admission in patients with ACS could predict the severity and complexity of coronary atherosclerosis together with multivessel disease, LVEF, and troponin levels. Thus, increased serum levels of hs-CRP were one of the strong predictors of high SXScore in ACS patients.