Objective. To study the effect of rosuvastatin on vascular biomarkers and carotid intima-media thickness (IMT) in systemic lupus erythematosus (SLE).Methods. SLE patients with inactive disease and subclinical atherosclerosis were randomized in a double-blinded manner to receive either rosuvastatin (10 mg/day) or matching placebo (half in each group were also randomly allocated low-dose aspirin). After 12 months, treatment was unblinded. Patients treated with rosuvastatin and aspirin were continued on the same medications for another 12 months. Plasma levels of homocysteine, high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule 1, P-selectin, and thrombomodulin were measured at baseline, 6 months, and 12 months. Measurement of carotid IMT was repeated at 24 months. Results. Seventy-two patients were studied (97% women, mean ؎ SD age 50.8 ؎ 9.7 years). Thirty-six patients were randomly assigned to each of the study arms (18 patients in each arm also received aspirin). Baseline clinical characteristics and medications were similar between the two groups. At 12 months, the mean low-density lipoprotein cholesterol (mean ؎ SD 2.62 ؎ 1.04 mmoles/liter to 1.69 ؎ 0.72 mmoles/liter; P < 0.001) and median hsCRP levels (1.26 mg/liter, interquartile range [IQR] 2.3 to 0.88 mg/liter, IQR 1.1; P ؍ 0.02) decreased significantly in the rosuvastatin group. There was no significant change in homocysteine, and aspirin use did not influence the levels of the biomarkers studied. A subgroup analysis of patients with a Systemic Lupus Erythematosus Disease Activity Index score <2 revealed a significant decrease in hsCRP (1.20 mg/liter, IQR 2.3 to 0.92 mg/liter, IQR 1.1; P ؍ 0.04) and thrombomodulin levels (0.76 ng/ml, IQR 1.2 to 0.67 ng/ml, IQR 1.0; P ؍ 0.001) with rosuvastatin treatment. At 24 months, the IMT of the internal carotid arteries appeared to be decreased in patients treated with rosuvastatin, which was well tolerated. Conclusion. In stable SLE patients, low-dose rosuvastatin leads to a significant reduction in hsCRP and thrombomodulin levels, which may possibly help to reduce cardiovascular risk.