Objective To investigate the relationship of serum γ-glutamyl transferase (γ-GT) and milk fat globule epidermal growth factor 8 (MFG-E8) levels with intravascular ultrasound imaging in patients with coronary atherosclerotic heart disease.Methods A total of 108 patients who underwent coronary angiography in our hospital from January to February 2018 were enrolled, 52 patients with stable angina pectoris served as control group and 56 patients with acute coronary syndrome as study group. All patients underwent intravascular ultrasound, and the plaque properties, thrombosis, and plaque rupture, as well as the differences in external imaging, eccentricity index, and vascular remodeling index were compared between the two groups. Serum γ-GT and MFG-E8 levels were measured at the same time. The differences in serum γ-GT and MFG-E8 expression levels were compared between different plaque properties, and the correlation between serum γ-GT and MFG-E8 levels was analyzed.Results The area of external elastic membrane of ACS patients was larger than that of SAP patients (P < 0.05), and the incidence of plaque rupture and thrombosis and positive remodeling index in ACS patients were higher than those in SAP patients (P < 0.05). The eccentricity index of patients with ACS was lower than that of patients with SAP (P < 0.05). In the two groups of patients with 154 arterial diseased plaques, the expression of γ-GT in hard plaques was higher than that in soft plaques (P < 0.05), and the expression level of MFG-E8 was lower than soft plaques (P < 0.05), and there were significant differences in the expression levels of γ-GT and MFG-E8 between the three plaques of atherosclerotic plaque (P < 0.05). Pearson correlation analysis showed that there was a negative correlation between the serum γ-GT and MFG-E8 expression levels in ACS patients (r = -0.923, P < 0.05).Conclusion Serum γ-GT and MFG-E8 are closely related to coronary arteriosclerosis and arterial calcification. The detection of serum γ-GT and MFG-E8 expression levels has important clinical significance for the diagnosis and prediction of the occurrence and development of coronary artery disease.