Aortic stiffness predicts cardiovascular mortality but is limited as a risk marker because it is dependent on blood pressure (BP). A potential solution is provided from the ratio of aortic-to-brachial artery stiffness (ab-ratio), which has been shown to be a BP-independent risk marker among patients with renal dysfunction (RD). We sought to determine the BP independence of the ab-ratio in patients with disease, including RD, and healthy populations. The ab-ratio (aortic/brachial pulse wave velocity) and mean arterial pressure (MAP) were recorded in patients with RD (n = 119, aged 65 ± 7 years), hypertension (n = 140, aged 62 ± 9 years), type 2 diabetes mellitus (n = 77, aged 60 ± 9 years) and healthy subjects (n = 99, aged 51 ± 8 years). Multiple-regression analysis was performed to test the independent association of MAP with the ab-ratio adjusted for age, sex, body mass index, glucose and heart rate. There was no significant relationship between the ab-ratio and MAP in patients with RD (β = 0.08, p = 0.34), hypertension (β = 0.04, p = 0.62) or diabetes (β = 0.22, p = 0.11). However, among healthy subjects the ab-ratio was significantly and independently associated with MAP (β = 0.31, p = 0.003). There was a significant difference in the strength of association between the ab-ratio and MAP between patients with disease and healthy subjects (z > 2.2, p < 0.05 all). Although ab-ratio is purported to be a risk marker that is independent of BP, this was observed only among patient populations, and not among healthy subjects. As a result, the ab-ratio has limited potential as a screening tool for the clinical assessment of arterial stiffness in otherwise healthy individuals.