Background: Highly-Sensitive C-reactive Protein (hs-CRP) levels are associated with short- and long-term mortality in patients with acute coronary syndrome (ACS). Aim: We investigated if baseline hs-CRP levels are correlated with burden of coronary atherosclerosis assessed by SYNTAX score (SXScore). Subjects and methods: We investigated 200 patients with ACS who underwent coronary angiography. The patients were divided into groups based on their SXScore: low SXScore (≤ 22), and intermediate-high SXScore (≥ 23). Results: Patients in the intermediate-high SXScore group had higher serum hs-CRP levels in comparison to low SXScore group (4.61 ±1.54 mg/dL versus 2.37 ± 0.66 mg/dL, P < 0.001). The mean age of patients and prevalence of diabetes in the intermediate-high SXScore group were statistically insignificantly than in the low SXScore group. Left ventricular ejection fraction (LVEF) was significantly lower in the patients with an intermediate-high SXScore (41±9 %) compared to low SXScore tertiles (50±8 %) (P< 0.001). There was significant correlation between the hs-crp levels and the syntax score. The correlation coefficient (r) = 0.567, also p value was significant p=0.0001. Consecutively hs-CRP at a cut-off point of ≥ 2.5mg/L was highly sensitive (97%) and specific (41%) and was a strongly independent predictor of a high SXScore in patients with ACS. Where accuracy of test was (acc= 0.94). Conclusion: It is believed that serum levels of hs-CRP on admission in patients with ACS thought to be a strong predictor of the severity and complexity of coronary atherosclerosis together with multivessel disease, and LVEF.