Objective To compare the effectiveness between doubled dose rosuvastatin and rosuvastatin combined with probucol for treatment of patients with coronary artery disease and hypercholesterolemia. Methods From Jan. 2012 to Dec. 2013, 68 patients with coronary heart disease, who were treated with rosuvastatin (10 mg qn) for more than 3 months in the Cardiology Clinic, Changhai Hospital and whose low density lipoprotein cholesterol (LDL-C) still not reached the target level, were evenly randomized into two groups: the double dose statin group (rosuvastatin 20 mg qn) and the combined treatment group (rosuvastatin 10 mg qn plus probucol 250 mg bid); the treatment lasted for 3 months. The peripheral blood lipid levels and incidence rates of adverse reactions were compared between the two groups. Results The baseline data and the lipid levels were not significantly different between the two groups before treatment (P>0.05). After 3 months of treatment, the total cholestrol (TC ) and LDL-C were significantly decreased in the two groups (P<0.05); triglyceride (TG) was significantly decreased only in the combined treatment group (P<0.05); the high-density lipoprotein cholesterol (HDL-C) had an increasing trend in the double rosuvastatin group and a decreasing one in the combined treatment group, but without statistical significance (P>0.05). Compared with the double rosuvastatin group, the combined treatment group had significantly greater decreases of TC and LDL-C (P<0.05), a significantly higher control rate of LDL-C (P<0.05), and a significantly lower HDL-C level (P<0.05). The combination treatment group had significantly less adverse reactions compared with the double rosuvastatin group (P<0.05). Conclusion For patients with coronary artery disease and hypercholesterolemia, it is more effective and safe to be treated with rosuvastatin combined with probucol than doubling the dose of rosuvastatin.