Background and aimsIt is unclear why blood pressure (BP), metabolic markers and smoking increase stroke incidence in women more than men. We examined these associations with carotid artery structure and function in a prospective cohort study. MethodsParticipants in the Australian Childhood Determinants of Adult Health study at ages 26–36 years (2004–06) were followed-up at 39–49 years (2014–19). Baseline risk factors included smoking, fasting glucose, insulin, systolic and diastolic BP. Carotid artery plaques, intima-media thickness [IMT], lumen diameter and carotid distensibility [CD] were assessed at follow up. Log binomial and linear regression with risk factor × sex interactions predicted carotid measures. Sex-stratified models adjusting for confounders were fitted when significant interactions were identified. ResultsAmong 779 participants (50% women), there were significant risk factor × sex interactions with baseline smoking, systolic BP and glucose associated with carotid measures in women only. Current smoking was associated with incidence of plaques (RRunadjusted 1.97 95% CI 1.4, 3.39), which reduced when adjusted for sociodemographics, depression, and diet (RRadjusted 1.82 95% CI 0.90, 3.66). Greater systolic BP was associated with lower CD adjusted for sociodemographics (βadjusted −0.166 95% CI -0.233, −0.098) and hypertension with greater lumen diameter (βunadjusted 0.131 95% CI 0.037, 0.225), which decreased when adjusted for sociodemographics, body composition and insulin (βadjusted 0.063 95% CI -0.052, 0.178). Greater glucose (βunadjusted −0.212 95% CI -0.397, −0.028) was associated with lower CD, which decreased when adjusted for sociodemographics, BP, depression and polycystic ovary syndrome (βadjusted −0.023 95% CI -0.249, 0.201). ConclusionsSmoking, SBP and glucose affect carotid structure and function more in women than men with some of this risk due to co-occurring risk factors.