We hypothesized that atorvastatin (ATOR) treatment would reduce arterial stiffness in overweight and obese middle-aged and older adults. Twenty-six (11 men and 15 women) overweight or obese (body mass index: 31.6+/-0.7 kg/m(2)) middle-aged and older adults (age: 54+/-2 years) were randomly assigned to receive either ATOR (80 mg/d) or placebo for 12 weeks. Arterial stiffness (beta-stiffness and pulse wave velocity) was measured before and after the intervention. At baseline, the ATOR (n=16) and placebo (n=10) groups did not differ with respect to age, body mass index, blood pressure, serum lipid and lipoprotein concentrations, high-sensitivity C-reactive protein, indices of arterial stiffness, or compliance (all P>0.05). After the 12-week treatment period, the ATOR group experienced a 47% reduction in low-density lipoprotein cholesterol (149+/-6 to 80+/-8 mg/dL) and a 42% reduction in high-sensitivity C-reactive protein (3.6+/-0.8 to 2.1+/-0.5 mg/L; both P<0.05). In addition, beta-stiffness (9.4+/-0.6 to 7.6+/-0.5 U) and aortic pulse wave velocity (1096+/-36 to 932+/-32 cm/s), but not brachial pulse wave velocity, decreased (both P<0.05) with ATOR. In contrast, there were no significant changes in beta-stiffness (9.1+/-0.8 to 9.1+/-0.7 U) or aortic pulse wave velocity (1238+/-89 to 1191+/-90 cm/s; both P>0.05) in the placebo group. There were no relations between the reductions in arterial stiffness indices and any of the baseline cardiometabolic risk factors (all P>0.05). However, the reductions in arterial stiffness were correlated with the reduction in low-density lipoprotein cholesterol but not high-sensitivity C-reactive protein or any other cardiometabolic variables (all P<0.05). Taken together, these findings suggest that ATOR reduces arterial stiffness in overweight and obese middle-aged and older adults, and these favorable changes occur irrespective of baseline cardiometabolic risk factors.