The menopausal transition is associated with increased risk for cardiovascular disease (CVD). Hot flashes (HF), a cardinal symptom of menopause, have been associated with increased CVD risk, particularly in perimenopausal women. Flow- mediated dilation (FMD) is an indicator of endothelial function and a sub-clinical CVD risk factor. Lower FMD has been associated with more HF. As moderate to vigorous physical activity (MVPA) is recognized to reduce CVD risk, our goal was to determine whether higher levels of MVPA change the relationship be-tween HF and FMD in perimenopausal women. Healthy perimenopausal women had HF measured objectively using sternal skin conductance for 24 h. MVPA was determined using 7 days of actigraphy. Endothelial function was measured via brachial artery FMD on the non-dominant arm. Pearson correlations and multiple regression analyses were used to evaluate relationships between variables. Simple slopes analysis was performed to understand how MVPA moderates the relationship between HF and FMD. Lower FMD tended to correlate with a higher objective HF rate, and this relationship was stronger for HF measured during waking hours. Controlling for age and BMI, HF and the interaction between HF and MVPA were significant predictors of FMD. Simple slope analysis showed a significant HF effect on FMD with lower (−1SD) MVPA, whereas there was no significant relationship between HF and FMD with higher (+1SD) MVPA. These results suggest that MVPA moderates the relationship between FMD and objective HFs in perimenopausal women