OBJECTIVE Several in vitro studies have reported on cavitation bubble visualization with mechanical heart valves and the cavitation intensity has been correlated with the design of the valve, the load on the valve occluder, the velocity of the occluder tip, and the negative pressure transients in the vicinity of the occluder. These studies demonstrated the presence of cavitation for certain types of valves under simulated normal physiological loading conditions. However, extrapolation of these results to cavitation initiation in vivo has been questioned due to limitations of the in vitro studies in simulating the in vivo tissue compliance. The present study was intended to analyze the effect of valve holder flexibility (simulating compliance of the suture ring and the surrounding tissue in vivo) on cavitation dynamics. METHODS Cavitation bubbles were visualized on three types of mechanical heart valves (Medtronic Hall, Edwards-Duromedics, and CarboMedics) in our in vitro set up, and pressure transients were measured close to the occluder at valve closure. Two different flexible valve holders made of Teflon (elastic modulus, E = 400 MPa) and low density polyethylene (E = 180 MPa) were employed and the results were compared with those with a rigid Plexiglas holder (E = 2930 MPa) of the same geometry (3'' by 3'' wide and 1/8'' thick). RESULTS Significant reductions were noted in the intensity of cavitation bubbles appearing along the clearance region of the Medtronic Hall and CarboMedics valves, with increasing valve holder flexibility. However, no attenuation was observed for the bubbles appearing around the seating lip or stop of the Edwards-Duromedics and Medtronic Hall valves that are believed to be caused by the fluid squeezing effect. CONCLUSIONS The results of the study suggest that timing of the mechanism to initiate cavitation is a critical factor in cavitation attenuation with flexible valve holders. If cavitation is initiated before the flexible valve holder responds to the impact at valve closure (such as due to squeeze film effect), cavitation intensity remains unchanged. Based on the results of the study, we propose that tissue compliance in vivo may not attenuate cavitation initiation for certain types of mechanical heart valves depending on the cavitation initiation mechanism.