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Mitochondria produce reactive oxygen species that may contribute to vascular dysfunction. α-Lipoic acid and acetyl-L-carnitine reduce oxidative stress and improve mitochondrial function. In a double-blind crossover study, the authors examined the effects of combined α-lipoic acid/acetyl-L-carnitine treatment and placebo (8 weeks per treatment) on vasodilator function and blood pressure in 36 subjects with coronary artery disease. Active treatment increased brachial artery diameter by 2.3% (P=.008), consistent with reduced arterial tone. Active treatment tended to decrease systolic blood pressure for the whole group (P=.07) and had a significant effect in the subgroup with blood pressure above the median (151±20 to 142±18 mm Hg; P=.03) and in the subgroup with the metabolic syndrome (139±21 to 130±18 mm Hg; P=.03). Thus, mitochondrial dysfunction may contribute to the regulation of blood pressure and vascular tone. Further studies are needed to confirm these findings and determine the clinical utility of α-lipoic acid/acetyl-L-carnitine as antihypertensive therapy.