Background: Physical performance measures have been shown to predict mortality and incident cardiovascular disease (CVD) mainly in elderly populations. We evaluated whether physical performance measures are associated with vascular health indices (carotid intima-media thickness (cIMT), adventitial diameter (cAD) and carotid plaque) in a large sample of multi-ethnic, late midlife women. Methods: Participants from the Study of Women's Health Across the Nation free of CVD and who had carotid ultrasound assessed at the 12th annual visit were evaluated. Physical function (PF) measures at visit 12 included: average 40-foot walking speed and average time needed for sit-to-stand assessment. Results: A total of 1103 women (53.7% White, 30.5% Black, 15.9% Chinese) aged 59.6 ± 2.7 years at visit 12, were included. In models adjusted for study site, race, current age, menopausal status and systolic blood pressure, slower walking speed and longer time needed for sit-to-stand were significantly associated with wider cAD, thicker cIMT and a higher probability of a high level of carotid plaque burden (all P-values < 0.05). Associations between walking speed and cAD, and between time needed for sit-to-stand and cAD, remained significant (P = 0.04) or marginally significant (P = 0.07), respectively, after additional adjustment for CVD risk factors, medications and physical activity. However, the associations between PF measures and cIMT and plaque burden were largely explained by traditional CVD risk factors. Conclusions: The current study suggests that worse performance in simple objective PF tests may be an early indicator of vascular structural changes that precede vascular disease among women at late midlife.