Abstract Background Congenital Heart Disease (CHD) predisposes to Infective Endocarditis (IE), but data about characterization and prognosis of IE in CHD patients is scarce. Methods The ESC-EORP-EURO-ENDO study is a prospective international study in IE patients (n = 3111). In this pre-specified analysis, adult CHD patients (n = 365, 11.7%) are described and compared with patients without CHD (n = 2746) in terms of baseline characteristics and mortality. Results CHD patients (73% men, age 44.8 ± 16.6 years) were younger and had fewer comorbidities. Of the CHD patients, 14% had a dental procedure before hospitalization versus 7% in non-CHD patients (p < 0.001) and more often had positive blood cultures for Streptococcus viridans (16.4% vs 8.8%, p < 0.001). As in non-CHD patients, IE most often affected the left-sided valves. For CHD patients, in-hospital mortality was 9.0% vs 18.1% in non-CHD patients (p < 0.001), and also, during the entire follow-up of 700 days, survival was more favorable (log-rank p < 0.0001), even after adjustment for age, gender and major comorbidities (Hazard Ratio (HR) 0.68; 95%CI 0.50–0.92). Within the CHD population, multivariable Cox regression revealed the following effects (HR and [95% CI]) on mortality: fistula (HR 6.97 [3.36–14.47]), cerebral embolus (HR 4.64 [2.08–10.35]), renal insufficiency (HR 3.44 [1.48–8.02]), Staphylococcus aureus as causative agent (HR 2.06 [1.11–3.81]) and failure to undertake surgery when indicated (HR 5.93 [3.15–11.18]). Conclusions CHD patients with IE have a better outcome in terms of all-cause mortality. The observed high incidence of dental procedures prior to IE warrants further studies about the current use, need and efficacy of antibiotic prophylaxis in CHD patients.