Recent studies have shown that rosuvastatin significantly decreases serum levels of inflammatory biomarkers and slows progression of carotid atherosclerosis in the general population. However, there are no data about its effect on progression of atherosclerosis in HIV-infected patients. Adult patients with HIV infection, on stable antiretroviral therapy, with asymptomatic carotid atherosclerosis and hypercholesterolemia, who started a rosuvastatin treatment at 10 mg daily during the period 2007-2009 were enrolled and followed-up for 24 months. Thirty-six patients (30 males) were enrolled, with a mean age of 49 years, a mean duration of current antiretroviral therapy of 38 months, and a mean 10-year risk of myocardial infarction of 18.5%. Rosuvastatin led to a significant decrease in mean values of intima-media thickness in all extracranial carotid arteries, with the greatest magnitude observed in carotid bifurcations (a mean decrease of 18.7% in the right artery and of 21.4% in the left artery) and in internal carotid arteries (a mean decrease of 23.7% in the right artery and of 25.6% in the left artery). Moreover, there was a significant reduction in mean levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides versus respective baseline values associated with a significantly decreased mean cardiovascular risk. The treatment with rosuvastatin was well tolerated, and serious adverse events were not reported. A 24-month treatment with rosuvastatin in HIV-infected patients on highly active antiretroviral therapy (HAART) with subclinical atherosclerosis and a moderate cardiovascular risk seems to promote significantly favorable changes in carotid atherosclerosis, associated with a favorable effect on serum lipid levels and a good tolerability profile.