Introduction: Elevated systolic blood pressure (SBP) during exercise is associated with abnormal vascular function and left ventricular (LV) hypertrophy. While women have lower exercise BP compared to men, few studies have explored the underlying sex differences associated with exercise BP response. We hypothesized women who generated higher exercise SBP would be more likely than men to have abnormal measures of cardiac and vascular stiffness as well as lower aerobic fitness, features associated with stage A HFpEF. Methods: We studied 85 (45% male) healthy normotensive middle aged subjects (53 ± 5 yrs). VO2 (Douglas bags) and BP (ECG gated electrosphygmomanometry) were measured at rest and maximal exercise. Resting cardiac function was assessed using echo (2D, 3D) and invasive measurement (right heart catheterization) of LV filling pressure under varying preloads. LV stiffness was calculated by curve fit of the diastolic portion of the pressure-volume curve. Aortic pulse wave velocity (PWV) and central aortic pressure were measured by arterial tonometry. Two factor ANCOVA was used to determine interaction between men and women using SBP as the independent variable. Results: In men, low fitness (peak VO2) was the best predictor of elevated exercise SBP. (R2 0.24) Similarly for women, fitness was predictive of exercise SBP in addition to vascular stiffness (PWV). (R2 0.55) When compared to men, women with elevated exercise SBP were distinctly more likely to have higher LV and vascular stiffness, impaired LV relaxation (IVRT; isovolumic relaxation time) as well as higher body fat percentage. (Table) Conclusions: In otherwise healthy middle aged women, elevated exercise BP was associated with increased LV and vascular stiffness, impaired LV relaxation and higher body fat, pre-clinical features consistent with stage A HFpEF. These relationships were not seen in men. Elevated exercise SBP in middle aged women may help identify a vulnerable population at risk for future HFpEF.