BACKGROUND: Patients with congenital heart disease (CHD) often require prosthetic valve implantation, increasing their lifetime risk of developing prosthetic valve endocarditis (PVE). The purpose of this study was to determine the incidence, risk factors, and outcomes of PVE in adults with CHD. METHOD: Retrospective cohort study of adults with CHD and prior prosthetic valve implantation (2003-2023). Patients diagnosed with PVE were designated as the PVE group, while the patients without PVE were designated as the reference group. RESULTS: Of 9161 patients, 3150 (34%) had prosthetic valves. Among the patients with prosthetic valve, 86 (2.7%) developed PVE, yielding an incidence of 5.2 (95% confidence interval [CI] 4.8-1-5.6) events per 1000 patient-years. Of the 86 patients with PVE, the average age at the time of PVE diagnosis was 35 ± 9 years, the average interval between prosthetic valve implantation and PVE was 91 ± 27 months, and mean duration of follow-up with11.6 ± 4.9 years. The risk factors for PVE were male sex, younger age, type 2 diabetes, multiple prosthetic valves, and Melody bioprosthetic valve implantation. PVE was associated with more than a 2-fold increase in all-cause mortality (adjusted hazard ratio 2.21, 95% CI 1.33-3.68, P = .002), after adjustment for demographic/anatomic indices, and comorbidities. Of 86 patients with PVE, 21 (24%) died during follow-up. The 30-day, 1-year, and 5-year mortality after diagnosis of PVE was 1.6%, 12% and 15%, respectively. Of 86 patients, 39 (45%) developed 47 PVE-related complications (perivalvular abscess[(n = 21], and septic emboli [n = 26]). PVE-related complications were associated with all-cause mortality. CONCLUSIONS: PVE was common in CHD patients with prosthetic valves and was associated with all-cause mortality. These findings highlight the prognostic implications of prosthetic valve implantation in patients with CHD, and the need for new criteria for risk stratification in order to improve outcomes.