OBJECTIVE: The menopausal transition has a negative effect on peripheral dilation in response to various stimuli including shear stress and exercise. Whether the presence of elevated traditional cardiovascular disease (CVD) risk factors in women going through menopause exacerbates the adverse effect on peripheral vasodilation is unclear. METHODS: Forty-four perimenopausal women with relatively low CVD risk were divided into tertiles based on atherosclerotic CVD (ASCVD) 10-year risk scores (lowest: 0.1%-0.5%, middle: 0.6%-0.9%, higher: >1%). Comparisons were made across tertile groups for the femoral artery vascular conductance (FVC) response to single-leg knee extension exercise (0, 5, 10, 15 W) as measured using Doppler ultrasound. RESULTS: At higher exercise intensities, FVC was lower in women in the tertile group with the highest ASCVD 10-year risk scores (10 W: 6 ± 2 mL/min/mm Hg, 15 W: 8 ± 3 mL/min/mm Hg) compared to women in the lowest tertile group (10 W: 9 ± 3 mL/min/mm Hg, P = 0.01; 15 W: 12 ± 3 mL/min/mm Hg, P < 0.01) and middle tertile group (10 W: 10 ± 4 mL/min/mm Hg, P < 0.01; 15 W: 12 ± 5 mL/min/mm Hg, P < 0.01). The overall increase in FVC during exercise from 0 to 15 W remained lower (P ≤ 0.01) in women with the highest ASCVD risk scores compared to the other two tertile groups even after adjustment for chronological age, arterial stiffness, and fat-free mass adjusted aerobic fitness level. CONCLUSION: Our results show that the presence of mild differences in ASCVD risk scores may be associated with a blunted active limb blood flow during leg exercise in mid-life women transitioning through menopause.