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The second heart sound (S2) is triggered by an aortic valve closure as a result of the ventricular-arterial interaction of the cardiovascular system. The objective of this paper is to investigate the timing of S2 in response to the changes in hemodynamic parameters and its relation to aortic blood pressure (BP). An improved model of the left ventricular-arterial interaction was proposed based on the combination of the newly established pressure source model of the ventricle and the nonlinear pressure-dependent compliance model of the arterial system. The time delay from the onset of left ventricular pressure rise to the onset of S2 (RS2) was used to measure the timing of S2. The results revealed that RS2 bears a strong negative correlation with both systolic blood pressure and diastolic blood pressure under the effect of changing peripheral resistance, heart rate, and contractility. The results were further validated by a series of measurements of 16 normal subjects submitted to dynamic exercise. This study helps understand the relationship between the timing of S2 and aortic BP under various physiological and pathological conditions.