Abstract Aims The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) European Endocarditis (EURO-ENDO) registry aims to study the care and outcomes of patients diagnosed with infective endocarditis (IE) and compare findings with recommendations from the 2015 ESC Clinical Practice Guidelines for the management of IE and data from the 2001 Euro Heart Survey. Methods and results Patients (n = 3116) aged over 18 years with a diagnosis of IE based on the ESC 2015 IE diagnostic criteria were prospectively identified between 1 January 2016 and 31 March 2018. Individual patient data were collected across 156 centres and 40 countries. The primary endpoint is all-cause mortality in hospital and at 1 year. Secondary endpoints are 1-year morbidity (all-cause hospitalization, any cardiac surgery, and IE relapse), the clinical, epidemiological, microbiological, and therapeutic characteristics of patients, the number and timing of non-invasive imaging techniques, and adherence to recommendations as stated in the 2015 ESC Clinical Practice Guidelines for the management of IE. Conclusion EURO-ENDO is an international registry of care and outcomes of patients hospitalized with IE which will provide insights into the contemporary profile and management of patients with this challenging disease.