Most techniques previously used to assess left ventricular (LV) end-systolic elastance (E(es)) and ventricular-arterial coupling (C(LV-A)) relied on invasive measurements and data acquisition over a wide range of loading conditions. Our goals were to 1) assess the feasibility of noninvasive assessment of E(es) and C(LV-A) using real-time three-dimensional echocardiography (RT3DE) and arterial tonometry; 2) test the ability of this approach to detect changes in LV contractility; and 3) study its reproducibility. We studied pharmacologically induced changes in inotropic state (5 and 10 μg·kg(-1)·min(-1) dobutamine) in normal volunteers (N = 8) and compared 10 normal volunteers with 10 patients with dilated cardiomyopathy (DCM; ejection fraction < 35%). RT3DE LV images, calibrated carotid artery tonometry, and Doppler tracings were obtained to noninvasively estimate E(es) and C(LV-A), using two alternative calculations. Dobutamine caused a significant stepwise increase in blood pressure, heart rate, ejection fraction, and E(es) and a decreased C(LV-A). In patients with DCM, E(es) was significantly reduced and C(LV-A) elevated, compared with controls. Both inter- and intraobserver variability were good for all measured parameters, as reflected by intraclass correlation coefficients (>0.8) and coefficients of variation (<20%). While both E(es) estimates showed significant differences between DCM patients and controls, one estimate resulted in no overlap and better reproducibility (interobserver intraclass correlation coefficient: 0.83 vs. 0.47, coefficients of variation: 20 vs. 29%). This is the first study to test the feasibility of using RT3DE-derived LV volumes in conjunction with arterial tonometry to noninvasively quantify LV elastance and C(LV-A). This approach was found to be sensitive enough to detect expected differences in LV contractility and reproducible. Due to its noninvasive nature, this methodology may have clinical implications in various disease states.