BackgroundCarotid intima-media thickness (cIMT) provides an index of arterial injury. Frailty is an indicator of vulnerability to adverse health outcomes. It is unclear whether cIMT is associated with the multi-dimensional frailty index and/or if this relationship is age- or sex-specific. The aim was to determine the impact of age and sex on the relationship between cIMT and frailty level in middle-aged and older adults. MethodsFrailty and cIMT data were extracted from the Canadian Longitudinal Study of Aging baseline comprehensive cohort of middle-aged (45–64 years) and older adults (>65 years) (n = 10,209). cIMT was assessed via high-resolution ultrasound. Frailty was determined using a 52-item index. Covariate-adjusted ordinary least squares regressions were conducted separately for middle-aged males (n = 3178), middle-aged females (n = 3125), older males (n = 2031), and older females (n = 1875). ResultsAverage cIMTs were larger in older versus middle-aged adults and in males versus females (all, p < 0.001). Average cIMT was positively associated with frailty level in adjusted linear regression models in middle-aged males [adj. R2 = 0.09; β = 0.015 (95 % CI: 0.005–0.026), p = 0.004], middle-aged females [adj. R2 = 0.11; β = 0.040 (95 % CI: 0.025–0.054), p < 0.001], older males [adj. R2 = 0.12; β = 0.019 (95 % CI: 0.004–0.034), p = 0.01], and older females [adj. R2 = 0.11; β = 0.020 (95 % CI: 0.002–0.039), p = 0.03]. ConclusioncIMT was an independent contributor to frailty level regardless of age group (middle-aged/older adults) or sex, with the strongest effect observed in middle-aged females. Our cross-sectional study documents the independent relationship between a marker of cardiovascular function and an increased vulnerability to adverse health outcomes in middle-aged and older males and females.