Background: Hypertension and diabetes mellitus frequently coexist; however, differences in the bi-directional longitudinal relationships of arterial stiffness with hypertension and diabetes mellitus have not yet been clarified. Methods: In this 16-year prospective observational study, 3981 middle-aged Japanese subjects without hypertension/diabetes mellitus at the study baseline underwent annual measurements of the blood pressure, serum glycosylated hemoglobin A1c (HbA1c), and brachial-ankle pulse wave velocity (baPWV). Results: By the end of the study period, 664, 779, 154 and 406 subjects developed hypertension, prehypertension, diabetes mellitus and prediabetes, respectively. Increased baPWV at the baseline was associated with a significant odds ratio for new onset of prehypertension/hypertension without (beta = 5.0 x 10–3, P < 0.01) or with (beta = 4.0 x 10–3, P < 0.01) coexisting prediabetes/diabetes mellitus; no such association was found with new onset of prediabetes/diabetes mellitus alone. Furthermore, baPWV showed significant longitudinal associations with the development of all of the above conditions. Conversely, elevated mean blood pressure, even in the pre-hypertensive range, showed a significant longitudinal association with increase of the baPWV. Conclusions: In middle-aged Japanese subjects, a vicious cycle may be triggered between elevated blood pressure, even from the prehypertensive stage, and arterial stiffening and development of diabetes mellitus may be observed as a cross phenomenon of this vicious cycle with a collateral event. Arterial stiffness may be a key element in the development of hypertension, so that its contribution to cardiovascular risk may be greater in patients with hypertension than in those with diabetes mellitus.