Background. Because severe aortic insufficiency in the setting of preserved left ventricular function is often associated with a long asymptomatic period and unpredictable course on medical therapy, sensitive indices of left ventricular systolic performance are necessary for the optimal direction of therapeutic intervention. Because myocardial wall stress is closely related to both pathologic cardiac remodeling and ultimately to left ventricular decompensation, an accurate description of regional wall stress distribution may improve our ability to clinically manage these patients appropriately. The objectives of this study were (1) to define sensitive, noninvasive indices of left ventricular systolic performance to assist the clinician in the serial evaluation and early detection of increased left ventricular wall stress and, therefore, inadequate left ventricular remodeling and subsequent myocardial decompensation of patients with aortic insufficiency, and (2) to quantify differences in instantaneous global and regional end-systolic wall stress between normal subjects and patients. Methods. Magnetic resonance imaging was performed on 23 normal volunteers and 19 patients with aortic insufficiency and normal systolic function (ejection fraction, 57% ± 6%). Finite-element analysis was used to estimate global and regional end-systolic stress. Results. End-systolic stress was significantly higher in the patient group globally (154,700 ± 31,711 versus 96,781 ± 23,185 dyne/cm2; p < 0.001) and regionally (p < 0.001 in all segments) despite normal systolic function and similar end-systolic pressures. Conclusions. End-systolic stress as determined by magnetic resonance imaging and finite-element analysis may have considerable potential as a noninvasive, clinically applicable index of regional left ventricular function that may help in the serial evaluation, optimal management, and early identification of left ventricular decompensation in patients with aortic insufficiency.