In vitro cardiovascular device performance evaluation in a mock circulation loop (MCL) is a necessary step prior to in vivo testing. A MCL that accurately represents the physiology of the cardiovascular system accelerates the assessment of the device's ability to treat pathological conditions. To serve this purpose, a compact MCL measuring 600 × 600 × 600 mm (L × W × H) was constructed in conjunction with a computer mathematical simulation. This approach allowed the effective selection of physical loop characteristics, such as pneumatic drive parameters, to create pressure and flow, and pipe dimensions to replicate the resistance, compliance, and fluid inertia of the native cardiovascular system. The resulting five-element MCL reproduced the physiological hemodynamics of a healthy and failing heart by altering ventricle contractility, vascular resistance/compliance, heart rate, and vascular volume. The effects of interpatient anatomical variability, such as septal defects and valvular disease, were also assessed. Cardiovascular hemodynamic pressures (arterial, venous, atrial, ventricular), flows (systemic, bronchial, pulmonary), and volumes (ventricular, stroke) were analyzed in real time. The objective of this study is to describe the developmental stages of the compact MCL and demonstrate its value as a research tool for the accelerated development of cardiovascular devices.