Aortic stenosis is the most common cardiovascular disease after systemic hypertension and coronary artery disease in developed countries. It induces an obstruction to blood flow from the left ventricle to the aorta resulting in an increase in left ventricular afterload. More than 30% of patients with aortic stenosis have concomitant systemic hypertension. In such patients, the left ventricle faces a double pressure overload (valvular and vascular). A detailed understanding of the respective impacts of aortic stenosis and hypertension on left ventricular function would help to better predict whether aortic valve replacement and/or antihypertensive medical treatment would be beneficial. To better understand how coexisting aortic stenosis and hypertension affect the left ventricular function, we developed a relatively simple mathematical cardiovascular model to simulate the ventricular-valvular-vascular hemodynamic interaction(V³ model). The present chapter provides a detailed description of the V³ model along with numerical findings as well as their clinical implications. Several simulations with the V³ model were performed to describe the effect of aortic stenosis on left ventricular stroke work and show the effect of coexistent systemic hypertension. Our simulations demonstrated that mild or moderate aortic stenosis has a small impact on left ventricular stroke work, whereas the latter increases noticeably when aortic stenosis becomes severe. They also showed that even mild hypertension may greatly influence left ventricular stroke work in patients with aortic stenosis. The mathematical V³ model thus provides a potentially useful tool to investigate complex cardiovascular interactions that could be of great clinical interest.