Cardiovascular stress reactivity is a predictor of atherosclerosis and cardiac events. Dehydroepiandrosterone (DHEA) protects against cardiovascular diseases, but results among previous studies have been inconsistent. We investigated the association between dehydroepiandrosterone-sulfate (DHEA-s) and cardiovascular stress reactivity in Japanese women and men. Among 979 healthy Japanese subjects (641 women and 338 men), serum levels of DHEA-s, systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, heart rate variability, and peripheral blood flow were measured under rest and two types of task. Mean differences in measured variables during tasks and a post-task period were calculated as changes in stress reactivity. Variables of stress reactivity were adjusted for multiple potential confounding factors. In women, DHEA-s levels showed positive associations with changes in SBP and DBP (standardized beta=0.12, p = 0.020; 0.17, 0.002, respectively). Stratification by menopausal status and other lifestyle factors (e.g., smoking status, alcohol consumption) were conducted. Significant positive associations remained in pre-menopausal (standardized beta = 0.13, p = 0.037; 0.18, 0.005), non-smoking (0.12, 0.010; 0.18, <0.001), and non-drinking women (0.14, 0.021; 0.21, 0.001), and women without a medical history (0.15, 0.020; 0.20, 0.001). In men, there was no significant association between DHEA-s levels and changes in stress reactivity. DHEA-s levels were positively associated with high blood-pressure reactivity to stress in women, and being menopausal, smoking, and alcohol consumption modified this association. (C) 2016 Elsevier Ltd. All rights reserved.