The use of compliance chambers in mock circulatory loop construction is the predominant means of simulating arterial compliance. Utilizing mock circulatory loops as bench test methods for cardiac assist technologies necessitates that they must be capable of reproducing the circulatory conditions that would exist physiologically. Of particular interest is the ability to determine instantaneous compliance of the system, and the ability to change the compliance in real-time. This capability enables continuous battery testing of conditions without stopping the flow to change the compliance chamber settings, and the simulation of dynamic changes in arterial compliance. The method tested involves the use of a compliance chamber utilizing a circular natural latex rubber membrane separating the fluid and air portions of the device. Change in system compliance is affected by the airspace pressure, which creates more reaction force at the membrane to the fluid pressure. A pressure sensor in the fluid portion of the chamber and a displacement sensor monitoring membrane center deflection allow for real-time inputs to the control algorithm. A predefined numerical model correlates the displacement sensor data to the volume displacement of the membrane. The control algorithm involves a tuned π loop maintaining the volume distention of the membrane via regulation of the air space pressure. The proportional integral (PI) controller tuning was achieved by creating a computational model of the compliance chamber using Simulink™ Simscape® toolboxes. These toolboxes were used to construct a model of the hydraulic, mechanical, and pneumatic elements in the physical design. Parameter Estimation™ tools and Design Optimization™ methods were employed to determine unknown physical parameters in the system, and tune the process controller used to maintain the compliance setting. It was found that the resulting control architecture was capable of maintaining compliance along a pressure-volume curve and allowed for changes to the compliance set point curve without stopping the pulsatile flow.