Accelerated testing (AT) of prosthetic heart valves allows simulation of wear and fatigue sustained by the replacement heart valves, and to estimate the valves’ life expectancy in human body. At accelerated test rates, sufficient amounts of data can be collected within a reasonably short time period, after repeated opening and closing cycles, to predict the valve durability. The U.S. Food and Drug Administration (FDA) Replacement Heart Valve Guidance (Version 4.1, 1994) requires that mechanical heart valves (MHV) must be tested at least 600 million cycles (equivalent to 15 years in vivo), while biological heart valve prostheses (BHV) must be tested at least 200 million cycles (equivalent to 5 years in vivo) in pulsatile flow simulators. The cyclic test must meet two basic FDA requirements: 1) the test valve open and close fully each cycle; and 2) the average transvalvular pressure is kept at least 100 mmHg at closure. At accelerated test rates, the valves were subjected to non-physiologic dynamic force loads and often damaged under excessive conditions, such as cavitation. AT may pinpoint early flaws in the design and in the manufacturing processes, and deflects regions of materials weakness. Hence the design of AT must follow the principles of engineering testing such as the law of dynamic similarities. One must first identify dimensionless parameters that are physiologically meaningful and those much be specific to heart valve testing. The main goal of this paper is to present an AT system and an experimental protocol so that in vitro accelerated testing may be carried out without creating these excess forces on the test valves and to predict the durability of prosthetic heart valves with physiological considerations.