BACKGROUND: The plasma cystatin C concentration (PcyC) has been demonstrated to have prognostic value in acute coronary syndrome, but the study of PcyC in patients with borderline coronary lesions is limited. Moreover, the effects of atorvastatin and probucol on PcyC and the severity of coronary lesions are unknown. This study was to evaluate the effects of the combination of atorvastatin and probucol on PcyC and severity of coronary lesion in patients with borderline coronary lesions. METHODS: One hundred and thirty consecutive patients with borderline coronary lesions (40% to 60% isolated single stenosis assessed by quantitative coronary angiography) were enrolled into the borderline coronary lesion (BCL) group, and one hundred and thirty-six subjects without coronary lesions comprised the controls (CTR). The subjects in the BCL group were randomized into routine treatment (RTT, n = 60), and combined treatment with atorvastatin 20 mg plus probucol 1.0 g daily added to routine medication (CBT, n = 70), both groups were treated for 6 months continuously. The levels of PcyC, high-sensitive C-reactive protein (hs-CRP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were determined. One hundred and four subjects in the BCL group were rechecked by coronary angiography. RESULTS: PcyC levels were significantly higher in the BCL group than in the CTR group; (2003.26 ± 825.73) ng/ml vs. (1897.83 ± 664.46) ng/ml (P < 0.01). Compared with patients in the RTT group, the levels of PcyC, TC, LDL-C, TG and hs-CRP were significantly lower in the CBT group (P < 0.05). Moreover, there was a trend towards a slight decrease in the RTT patients, (54.38 ± 10.67)% vs. (50.29 ± 9.89)% (P > 0.05), and a significant decrease in the CBT patients, (53.65 ± 9.48%) vs. (40.38 ± 12.93)% (P < 0.05), in the mean percent stenosis of borderline coronary lesions before and after six months of treatment. CONCLUSIONS: Cystatin C played an important role in the development of coronary artery disease, and was associated with the severity of coronary lesions. The combination of atorvastatin and probucol decreased PcyC levels, and could be the treatment of choice.