In patients with aortic stenosis, the left ventricular afterload is determined by the degree of valvular obstruction and the systemic arterial system. We developed an explicit mathematical model formulated with a limited number of independent parameters, which describes the interaction between the left ventricle, an aortic stenosis and the arterial system. This ventricular-valvular-vascular (V³) model consists of the combination of the time-varying elastance model for the left ventricle, the instantaneous transvalvular pressure-flow relationship for the aortic valve and the three-element Windkessel representation of the vascular system. The objective of this study was to validate the V³ model using pressure-volume loop data obtained in 6 patients with severe aortic stenosis, before and after aortic valve replacement. There was a very good agreement between the estimated and the measured left ventricular and aortic pressure waveforms. The total relative error between estimated and measured pressures was on average (± standard deviation) 7.5 ± 2.3% and the equation of the corresponding regression line was y = 0.99 x − 2.36 with a coefficient of determination r² = 0.98. There was also a very good agreement between estimated and measured stroke volumes (y = 1.03 x + 2.2, r² = 0.96, SEE = 2.8 mL). Hence, this mathematical V³ model can be used to describe the hemodynamic interaction between the left ventricle, the aortic valve, and the systemic arterial system.