Background— Prosthesis-patient mismatch (P-PtM) after aortic valve replacement results in disturbed valve performance associated with increased pressure gradients. However, it is unknown whether this can be related to future structural valve deterioration (SVD) of the bioprosthesis. Methods and Results— In 564 patients (mean age, 74±5 years) receiving an aortic valve bioprosthesis, clinical follow-up (median, 6.1 years; maximum, 16.4 years) was analyzed including echocardiography. SVD was diagnosed in 40 patients (7%) as substantially increased stenosis (n=24) or regurgitation (n=16) of the operated valve over time. When patients with P-PtM (effective orifice area index <0.85 cm 2 /m 2 ; n=285) developed SVD, it was preferentially of the stenosis type, whereas when patients without P-PtM (n=279) developed SVD, the majority was of the incompetence type ( P <0.05). Multivariable analysis including patient- and valve-related variables revealed that P-PtM and label size ≤21 were independent predictors of SVD ( P =0.04 and P =0.02, respectively). A nonparametric Turnbull estimate analysis showed that SVD is virtually nonexistent for up to 9 years in patients without P-PtM. Thereafter, SVD starts to occur and is mainly of the incompetence-type SVD (79% of cases). In patients with P-PtM, SVD starts to occur after 2 to 3 years after implantation and is mainly of the stenosis-type SVD (81% of cases). Conclusions— These data suggest that stenosis-type SVD is an early, P-PtM–related, and thus preventable phenomenon. Incompetence-type SVD is a time-dependent, nonspecific wear damage to bioprosthetic valves, which is not related to P-PtM.