Objectives: Patient-prosthesis mismatch (PPM) may impair functional capacity and survival after aortic valve replacement (AVR). A mechanical prosthesis tends to have less PPM than a biological prosthesis, but these differences in clinical outcomes remain unclear. This study aimed to investigate the impact of PPM on long-term survival and quality of life (QoL) after mechanical and biological AVRs. Methods: The presence of PPM was defined in 595 consecutive patients who had undergone isolated AVR. Patients were divided into two groups according to whether they had received a biological or mechanical prosthesis. The groups with and without PPM present were compared with regard to baseline characteristics, operative characteristics, survival, severe complications, freedom from angina and QoL up to 6 years of follow-up. PPM calculation was performed using the EOA value provided by the manufacturer for every prosthesis divided by the patient’s body surface area. Results: The moderate-to-severe PPM rates were 69.8% and 3.7% after biological and mechanical prostheses implantation, respectively. Patients with a biological prosthesis implanted had mean survival significantly shorter in the PPM group (50.2 months, 95% confidence interval [CI] 45.2-55.3) when compared to the no-PPM group (60.1 months, 95% CI 55.7-64.4) (p = 0.035). In the mechanical prosthesis group, there was no difference in mean survival between the PPM group (66.6 months, 95% CI 58.3-74.9) when compared to the no-PPM group (64.9 months, 95% CI 62.6-67.2) (p = 0.50). The physical score of the QoL questionnaire was significantly lower in the PPM group when compared to the no-PPM group with a biological prosthesis (39.4 ± 8.4 vs. 45.7 ± 10.1, p < 0.001) compared to patients with a mechanical prosthesis (43.9 ± 9.4 vs. 46.9 ± 8.3, p = 0.18). Conclusions: PPM is common after biological valve implantation and significantly impacts long-term survival and QoL. If the risk of PPM after implantation of a biological prosthesis is suspected, prospective strategies to avoid PPM at the time of operation are warranted.