Objective. To investigate the effects of low-density lipoprotein cholesterol (LDL-C) and serum cystatin C (CysC) combined with D-dimer (D-D) on patients with coronary atherosclerotic heart disease (CHD). Methods. 90 patients with CHD who were admitted to our hospital and diagnosed by coronary angiography (CAG) from February 2020 to June 2021 were selected as the study subjects. 90 patients were grouped according to different types and branches of coronary lesions, and 30 patients with outpatient health check-ups at the same period were selected as the control group, and the differences in serum LDL-C, CysC, and D-D levels between the groups were compared. The logistic regression model was built to explore risk factors affecting the occurrence of CHD. Also, receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic value of LDL-C, CysC, and D-D in CHD. Results. In the comparison of LDL-C, CysC, and D-D levels, CHD group > control group (
P
<
0.05
); stable angina (SAP) group > unstable angina (UAP) group > acute myocardial infarction (AMI) group (
P
<
0.05
); three-branch group > two-branch group > single-branch group (
P
<
0.05
). The logistic regression model showed that high expression levels of LDL-C, CysC, and D-D, male gender, and combined hypertension were risk factors for CHD. The area under the curve (AUC) of the combination of LDL-C, CysC, and D-D was 0.868, and the sensitivity and specificity were 88.89% and 73.33%, respectively, which are higher than those in single diagnosis (
P
<
0.05
). Conclusions. LDL-C, CysC, and D-D are highly expressed in CHD samples, and the combination of the three is beneficial to enhance the diagnostic accuracy of clinical CHD.