Objective To investigate the correlation between thrombelastography (TEG) and the severity of coronary artery lesions in patients with acute coronary syndrome (ACS). Methods A total of 130 patients admitted to the Department of Cardiology of our hospital who underwent coronary angiography and had positive results were consecutively recruited as the ACS group. Meanwhile, 86 patients with ACS excluded by coronary angiography during the same period were selected as the control group. TEG parameters [reaction time (R time), clotting time (K time), blood clot formation rate (Angle α), maximum amplitude (MA)], triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, lactate dehydrogenase, and platelet levels were measured for all subjects. The differences in TEG indicators between the ACS group and control group were compared to identify potential risk factors for ACS. In ACS patients, the correlations of TEG parame-ters with laboratory-related indicators and the severity of coronary artery lesions assessed by the Gensini score were evalua-ted and analyzed. Logistic regression analysis was employed to evaluate the influencing factors of TEG in ACS patients with different numbers of coronary artery lesions. After adjusting for confounding factors, the independent predictive effect of TEG on the risk of ACS was further evaluated. Results The TEG parameters (R time and K time) in the ACS group were lower than those in the control group, and the difference was statistically significant (P<0.01). TEG parameters (R time and K time) were negatively correlated with the Gensini score (r_{R time}=-0.302 3, r_{K time}=-0.257 4, P<0.01). Multivariate logistic regression analysis showed that after adjusting for confounding factors, when TEG (K time) was considered as a categorical variable, Q4 (K time >2.10) was an independent protective factor against ACS (OR=0.34, 95% CI: 0.13-0.87, P<0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of R time and K time for diagnosing ACS was 0.781 0 and 0.605 1, respectively. The TEG parameter (R time) showed a sensitivity of 73.26% and a specificity of 70.00% for diagnosing ACS, while the K time showed a sensitivity of 65.38% and a specificity of 60.47%. Conclusion TEG is associated with ACS and the severity of coronary artery lesions and may serve as an independent predictor of the severity of coronary artery lesions in patients with ACS, which can provide a strong basis for determining whether further invasive diagnosis is needed.