BACKGROUND: The coexistence of hypertension and dyslipidemia synergistically increases the risk of cardiovascular events. We investigated the effect of the lipid-lowering agent micronized fenofibrate on inhibition of carotid atherosclerosis in patients with essential hypertension and mild hyperlipidemia. METHODS: We measured serum lipid profiles and inflammatory markers on chemistry or immune analyzers and common or internal carotid intima-media thickness (IMT) and diameter (D) by ultrasonography. RESULTS: Patients receiving micronized fenofibrate for 24 months in addition to antihypertensive treatment had decreased concentrations of total cholesterol, LDL-cholesterol, triglyceride, apolipoprotein B100, oxidized LDL, high-sensitivity C-reactive protein, P-selectin, and cytokines. These patients had increased concentrations of HDL-cholesterol, apolipoprotein A-I, and nitric oxide. Common carotid artery IMT (CCAIMT) and internal carotid artery IMT (ICAIMT) remained unchanged during the 24-month intervention. Moreover, the mean CCAIMT/D ratio and ICAIMT/D ratio were significantly decreased in the fenofibrate intervention group. In contrast, CCAIMT/D and ICAIMT/D ratios were increased in the control group. The incidence rates of carotid artery plaque formation and stroke in the fenofibrate intervention group were significantly lower than those in the control group. CONCLUSION: The combination of antihypertensive agents with micronized fenofibrate can effectively prevent the progression of carotid atherosclerosis and reduce the incidence of stroke in patients with essential hypertension.