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Early diastolic mitral annular velocity (E') by tissue Doppler echocardiography (TD) has been reported to be a load-independent index of left ventricular (LV) diastolic function, allowing the early diastolic mitral inflow velocity (E)/E' ratio to be used clinically to predict LV filling pressures. However, preload independence of E' has remained controversial, and E/E' may not consistently be predictive of LV filling pressures. Our objectives were to test the hypotheses that E' is affected by preload, and that alterations of preload, afterload, and contractility also affect E/E'. DESIGN, INTERVENTIONS, AND MEASUREMENTS: An open-chest dog model was used (n = 8). High-fidelity pressure and conductance catheters were used for pressure-volume relations, and E' was obtained by pulsed TD from the apical four-chamber view. Changes in preload and afterload were induced by vena caval and partial aortic occlusions, respectively. Data were collected during control phase and during infusions of dobutamine and esmolol to alter contractility. ⋯ E' was significantly influenced by preload with preserved LV function and low filling pressures (< 12 mm Hg); accordingly, E/E' was less predictive of LV filling pressures in this scenario. E/E' was more predictive of LV filling pressures in the presence of diastolic dysfunction.