This study explored the effects of probucol on atherosclerotic plaques and soluble thrombomodulin in patients with coronary heart disease (CHD). Five hundred and eighty-three patients with CHD who were admitted to Jining First People's Hospital from February 2013 to February 2014. A total of 300 of them received conventional treatment, and were assigned to the control group, while the remaining 283 patients were treated with probucol in addition to the conventional treatment, and were assigned to the observation group. A retrospective analysis was performed on the total cholesterol levels, atherosclerotic plaque sizes, and soluble thrombomodulin levels. Probucol was administered at a dose of 500 mg twice a day for a period of 16 weeks. The total cholesterol level decreased gradually over time during the treatment. After 8 weeks of treatment, the total cholesterol level in the observation group was lower than that in the control group (P<0.05). After 8 weeks of treatment, the atherosclerotic plaque area in the observation group decreased compared with that before treatment (P<0.05). After 8 and 16 weeks of treatment, the plaque area in the observation group was smaller than that in the control group (P<0.05). The soluble thrombomodulin level at any time-point after treatment was lower than that before treatment in both groups (P<0.05). At the same time-point, the level in the observation group was lower than that in the control group (P<0.05). The total cholesterol and soluble thrombomodulin levels were positively correlated with the atherosclerotic plaque area (r=0.841, P=0.001; r=0.725, P=0.008). When patients with CHD were treated with probucol in addition to the conventional treatment, a reduction of the atherosclerotic plaque area, as well as a decrease of both the total cholesterol and soluble thrombomodulin levels, was observed. Overall, patients with CHD experienced improved symptoms following treatment with probucol.