OBJECTIVE: Patients with the metabolic syndrome often have abnormal levels of proinflammatory and pro-oxidative mechanisms within their vasculature. We sought to determine whether the ACE inhibitor quinapril regulates markers of oxidative stress in the metabolic syndrome. RESEARCH DESIGN AND METHODS: Forty patients with the metabolic syndrome were randomized in a double-blind manner to either the ACE inhibitor quinapril (20 mg/day) or matching placebo for 4 weeks. Serum markers of vascular oxidative stress were measured. RESULTS: After 4 weeks of therapy, serum 8-isoprostane was reduced by 12% in the quinapril group when compared with placebo (quinapril, 46.7 +/- 1.0; placebo, 52.7 +/- 0.9 pg/ml; P = 0.001). Erythrocyte superoxide dismutase activity increased 35% in the quinapril group when compared with placebo (quinapril, 826.3 +/- 17.1; placebo, 612.3 +/- 6.9 units/g Hb; P < 0.001). In addition, lag time to oxidation of LDL, a marker of oxidative stress, was increased by 48% in the quinapril group when compared with placebo (quinapril 89.2 +/- 9.2 vs. placebo 60.1 +/- 12.3 min; P < 0.001). Therapy with quinapril was well tolerated. CONCLUSIONS: The addition of the ACE inhibitor quinapril reduces markers of vascular oxidative stress and may attenuate the progression of the pathophysiology seen in the metabolic syndrome.