Background: Native (NVE) and prosthetic (PVE) aortic valve endocarditis (AVE) remain a surgical challenge with an ongoing trend towards more complex surgical procedures. Methods: First-time NVE was compared with PVE, focusing on pathogens, risk factors, perioperative course, postoperative follow-up, including recurrent infection, as well as health-related quality of life (HRQOL). Results: From 2007 to 2022, surgical intervention for AVE was necessary in 231 patients with 233 episodes of infective aortic valve endocarditis, i.e., there were only two cases of reinfection (NVE group). The study group consisted of 130 cases with NVE and 103 with PVE. Overall, a median of 40.3% of survivors were in NYHA class I or II. In-hospital mortality was higher in the PVE group with 13.3%. The most common pathogen was Staphylococcus aureus, with 24.9% across both groups. EuroSCORE II was higher in the PVE group (19.0 ± 14.3% total, NVE 11.1 ± 8.1%, PVE 27.8 ± 14.6%; p < 0.05), reflecting an older, more co-morbid patient cohort. Abscess formation was also more common in the PVE group, while vegetations were more common in the NVE group. The 5-year and 10-year survival rates did not differ significantly between NVE and PVE and were 74.4% and 52.2% for the NVE group, respectively, and 67.4% and 52.9% for the PVE group, respectively. The HRQOL as assessed by the Minnesota Living with HF Questionnaire (MLHFQ) demonstrated no significant difference between both groups. Conclusions: Long-term survival and QoL after surgical treatment of infective aortic valve endocarditis are excellent and do not depend on the type of replacement.