Introduction: A resting supine pulmonary capillary wedge pressure (rsPCWP) of ≥ 15 mmHg measured by right heart catheterization is considered the hemodynamic “gold standard” diagnostic criteria for heart failure with preserved ejection fraction (HFpEF). However, right heart catheterization is typically performed as a one-time measurement in patients in the supine position. In this study we sought to define the degree to which PCWP changes upon assuming upright posture in HFpEF vs. controls and determinants of postural changes in PCWP. Hypothesis: Patients with elevated rsPCWP will experience a greater fall in PCWP upon assuming upright posture compared to controls and the degree of reduction will be proportionate to BMI. Methods: We performed supine right heart catheterization as well as seated upright hemodynamic measurements in consecutive patients referred to a single center for evaluation of exertional dyspnea. Patients with HFpEF as defined by symptoms and rsPCWP≥15mmHg were compared to controls with normal resting hemodynamics and normal exercise capacity. αPCWP was defined as rsPCWP - upright PCWP. Multivariate linear regression was performed with log transformation of non-normal data. Results: In 209 patients with HFpEF (age 61 + 14, 52% female, BMI 32 + 7) the mean αPCWP was 11.0+4.5 mmHg compared to 3.7mmHg in the control cohort (n=46, age 56 + 18, 57% female, BMI 26.9 + 4, p<0.001). BMI, but not age or sex were associated with αPCWP in HFpEF. After further adjustment for resting PCWP and blood pressure, BMI remained directly related to αPCWP in the HFpEF cohort (p<0.001). NTproBNP levels were significantly related to upright but not supine PCWP in HFpEF. Conclusion: In individuals who meet resting hemodynamic criteria for HFpEF, changes in PCWP with upright positioning are highly variable and change proportionate to BMI.