Load-adjusted measures of left ventricle (LV) systolic performance are limited by dependence on LV stiffness and afterload. To our knowledge, no stiffness-adjusted and afterload-adjusted indicator was tested in models of pressure (POH) and volume overload hypertrophy (VOH). We hypothesized that wall stress reflects changes in loading, incorporating chamber stiffness and afterload; therefore, stroke volume-to-wall stress ratio more accurately reflects systolic performance. We used rat models of POH (ascending aortic banding) and VOH (aorto-cava shunt). Animals underwent echocardiography and pressure-volume analysis at baseline and dobutamine challenge. We achieved extreme bidirectional alterations in LV systolic performance, end-systolic elastance (Ees), passive stiffness, and arterial elastance (Ea). In POH with LV dilatation and failure, some load-independent indicators of systolic performance remained elevated compared with controls, while some others failed to decrease with wide variability. In VOH, most, but not all indicators, including LV ejection fraction, were significantly reduced compared with controls, despite hyperdynamic circulation, lack of heart failure, and preserved contractile reserve. We related systolic performance to Ees adjusted for Ea and LV passive stiffness in multivariate models. Calculated residual Ees was not reduced in POH with heart failure and was reduced in VOH, while it positively correlated to dobutamine dose. Conversely, stroke volume-to-wall stress ratio was normal in compensated POH, markedly decreased in POH with heart failure, and, in contrast with LV ejection fraction, normal in VOH. Our results support stroke volume-to-wall stress ratio as a load-adjusted and stiffness-adjusted indicator of systolic function in models of POH and VOH.