African-American women have elevated rates of cardiovascular disease compared with women of other races or ethnicities, and race/ethnicity-related stressors may play a role. We examined the association between a race/ethnicity-related stressor, midlife loss, and a marker of cardiovascular risk, carotid intima media thickness (IMT), in 1,410 African-American, White, Chinese, and Hispanic women from the Study of Women's Health Across the Nation. Participants were queried about losses annually over 12 years (1996-2013), with IMT assessed in year 12-13 via ultrasound. Linear regression models were used to examine associations between cumulative upsetting losses and IMT, adjusting for covariates. In minimally adjusted models in the full cohort, 3 or more upsetting losses (vs. none) were associated with IMT (beta = 0.03, 95% confidence interval (CI): 0.01, 0.05; P = 0.0003). Results were more robust among African-American women (beta = 0.042, 95% CI: 0.01, 0.07; P < 0.01) than White (beta = 0.014, 95% CI: -0.01, 0.03; P = 0.21), Chinese (beta = 0.036, 95% CI: -0.03, 0.10; P = 0.25), or Hispanic (beta = 0.036, 95% CI: -0.07, 0.14; P = 0.51) women, although associations among women from racial/ethnic minorities overall were of similar magnitude. Results persisted in fully adjusted models (P for interaction with race/ethnicity = 0.04). Midlife loss may be a pathway through which race/ethnicity influences cardiovascular risk for African-American women and, potentially, Chinese and Hispanic women.