BACKGROUND Although high left ventricular filling pressures [left ventricular (LV) end-diastolic pressure or pulmonary capillary wedge pressure (PCWP)] are widely taken as surrogates for LV diastolic dysfunction, the actual distending pressure that governs LV diastolic stretch is transmural pressure difference (∆PTM). Clinically, preferring ∆PTM over PCWP may improve diagnostic and therapeutic decision-making. We aimed to compare the clinical implications of diastolic function characterization based on PCWP or ∆PTM. METHODS We retrospectively screened our hospital database for adult patients with a clinical diagnosis of heart failure who underwent right heart catheterization. Echocardiographic diastolic dysfunction was graded according to the current guidelines. LV end-diastolic properties were assessed with construction of complete end-diastolic pressure-volume relationship (EDPVR) curves using the single-beat method. Survival status was checked via the electronic national health-care system. RESULTS A total of 693 cases were identified in our database; the final study population comprised 621 cases. ∆PTM-based, but not PCWP-based, EDPVR diastolic stiffness constants were significantly predictive of advanced diastolic dysfunction. PCWP-based diastolic stiffness constants were not able to predict 5-year mortality, whereas ∆PTM-based EDPVR stiffness constants and volumes all turned out to have significant predictive power for 5-year mortality. CONCLUSIONS Left ventricular diastolic function assessment can be improved using ∆PTM instead of PCWP. As ∆PTM ultimately linked to right-sided functions, this approach emphasizes the limitations of taking LV diastolic function as an isolated phenomenon and underlines the need for a complete hemodynamic assessment involving the right heart in therapeutic and prognostic decision-making processes.