Objective: To investigate the clinical value of digital subtraction angiography (DSA) in the diagnosis of coronary artery disease (CAD) and to evaluate the diagnostic performance of serological parameters relative to the DSA gold standard. Methods: A total of 100 patients with confirmed CAD were included in this study. The case group comprised 100 patients with CAD confirmed by DSA, while the control group consisted of 100 age- and sex-matched individuals who underwent DSA during the same period and were excluded from CAD. DSA was employed to assess the degree and location of coronary artery stenosis. Retrospective collection and comparative analysis of serological parameters (cTnI, CK-MB, hs-CRP, LDL-C, TC) were performed between the two groups. The diagnostic efficacy of these serological indicators for CAD was calculated, and subgroup analyses were conducted to explore potential sex-related differences. Results: The case and control groups were comparable in baseline characteristics such as sex, age, and BMI (P > 0.05). Using DSA as the gold standard, the sensitivity and specificity of cTnI for diagnosing CAD were 82.0% and 85.0%, respectively; hs-CRP demonstrated a sensitivity of 85.0% and specificity of 75.0%. Levels of cTnI and hs-CRP increased significantly with the severity of coronary stenosis (P < 0.05). No statistically significant differences were observed between male and female subgroups (P > 0.05). Conclusion: DSA provides definitive assessment of lesion location, morphology, and number in coronary artery disease, with no significant sex-related differences. Serological markers, particularly cTnI and hs-CRP, demonstrate good auxiliary diagnostic value for CAD. Their levels correlate with disease severity and may serve as effective screening tools prior to DSA, offering important reference value for subsequent clinical management.