Undetected high risk for premature death of cardiovascular disease (CVD) among individuals with low-to-moderate risk factor scores is an acknowledged obstacle to CVD prevention. The vasculature\'s functional robustness against risk factor derailment may serve as a novel discriminator of mortality risk under similar risk factor loads. To test this assumption, we hypothesized that the expected inverse robustness-mortality association is verifiable as a significant trend along the age spectrum of risk factor-challenged cohorts. This is a retrospective cohort study of 372 adults (mean age 56.1 years, range 21-92; 45% female) with a variety of CV risk factors. An arterial model (VascAssist 2, iSYMED GmbH, Germany) was used to derive global parameters of arterial function from non-invasively acquired pulse pressure waves. Participants were stratified by health status: apparently healthy (AH; n = 221); with hypertension and/or hypercholesterolemia (CC; n = 61); with history of CV event(s) (CVE; n = 90). Multivariate linear regression was used to derive a robustness score which was calibrated against the CVD mortality hazard rate of a sub-cohort of the LURIC study (n = 1369; mean age 59.1 years, range 20-75; 37% female). Robustness correlated linearly with calendar age in CC (F(1, 59) = 10.42; p < 0.01) and CVE (F(1, 88) = 40.34; p < 0.0001) but not in the AH strata, supporting the hypothesis of preferential elimination of less robust individuals along the aging trajectory under risk factor challenges. Vascular robustness may serve as a biomarker of vulnerability to CVD risk factor challenges, prognosticating otherwise undetectable elevated risk for premature CVD mortality.