Mechanical circulatory support technology is continually improving. However, adverse complications do occur with devastating consequences, for example, pump thrombosis that may develop in several parts of the pump system. The aim of this study was to design an experimental clot/thrombosis model to register and analyze acoustic signals from the left ventricular assist device (LVAD) HeartMate II (HMII) (Thoratec Corporation, Inc., Pleasanton, CA, USA) and detect changes in sound signals correlating to clots in the inflow, outflow, and pump housing. Using modern telecom techniques, it was possible to register and analyze the HMII pump-specific acoustic fingerprint in an experimental model of LVAD support using a mock loop. Increase in pump speed significantly (P < 0.005) changed the acoustic fingerprint at certain frequency (0–23 000 Hz) intervals (regions: R1–3 and peaks: P1,3–4). When the ball valves connected to the tubing were narrowed sequentially by ∼50% of the inner diameter (to mimic clot in the out- and inflow tubing), the frequency spectrum changed significantly (P < 0.005) in P1 and P2 and R1 when the outflow tubing was narrowed. This change was not seen to the same extent when the lumen of the ball valve connected to the inflow tube was narrowed by ∼50%. More significant (P < 0.005) acoustic changes were detected in P1 and P2 and R1 and R3, with the largest dB figs. in the lower frequency ranges in R1 and P2, when artificial clots and blood clots passed through the pump system. At higher frequencies, a significant change in dB figs. in R3 and P4 was detected when clots passed through the pump system. Acoustic monitoring of pump sounds may become a valuable tool in LVAD surveillance.