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Introduction and Objectives: The variation between rest and peak stress end-systolic pressure-volume relation is an afterload-independent index of left ventricular contractility. Whether and to what extent it depends on end-diastolic volume remains unclear. The aim of this study was to assess the dependence of the delta rest-stress end-systolic pressure-volume relation on end-diastolic volume in patients with negative stress echo and all ranges of resting left ventricular function., Methods: We analyzed interpretable data obtained in 891 patients (593 men, age 63 ± 12 years) with ejection fraction 47% ± 12%: 338 were normal or near-normal or hypertensive; 229 patients had coronary artery disease; and 324 patients had ischemic or nonischemic dilated cardiomyopathy. They were studied with exercise (n = 172), dipyridamole (n = 482) or dobutamine (n = 237) stress echocardiography. The end-systolic pressure-volume relation was evaluated at rest and peak stress from raw measurement of systolic arterial pressure by cuff sphygmomanometer and end-systolic volume by biplane Simpson rule 2-dimensional echocardiography., Results: Absolute values of delta rest-stress end-systolic pressure-volume relation were higher for exercise and dobutamine than for dipyridamole. In the overall population, an inverse relationship between end-systolic pressure-volume relation and end-diastolic volume was present at rest (r 2 = 0.69, P < .001) and peak stress (r 2 = 0.56, P < .001), but was absent if the delta rest-stress end-systolic pressure-volume relation was considered (r 2 = 0.13)., Conclusions: Left ventricular end-diastolic volume does not affect the rest-stress changes in end-systolic pressure-volume relation in either normal or abnormal left ventricles during physical or pharmacological stress., (Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)