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Aims: The NatIonal Danish endocarditis stUdieS (NIDUS) registry aims to investigate the mechanisms contributing to the increasing incidence of infective endocarditis (IE) and to discover risk factors associated to the course, treatment and clinical outcomes of the disease., Methods: The NIDUS registry was created to investigate a nationwide unselected group of patients hospitalized for IE. The National Danish healthcare registries have been queried for validated IE diagnosis codes (International Classification of Disease, 10 th edition [ICD-10]: DI33, DI38, and DI398). Subsequently, a team of 28 healthcare professionals, including experts in endocarditis, will systematically review and evaluate all identified patient records using the modified Duke Criteria and the 2015 European Society of Cardiology modified diagnostic criteria. The registry will contain all cases with definite or possible IE found in primary data sources in Denmark between January 1, 2016, and December 31, 2021. We will gather individual patient data, such as clinical, microbiological, and echocardiographic characteristics, treatment regimens, and clinical outcomes. A digital data collection form will be used to the gathering of data. A sample of approximately 4,300 individual patients will be evaluated using primary data sources., Conclusions and Perspectives: The NIDUS registry will be the first comprehensive nationwide IE registry, contributing critical knowledge about the course, treatment, and clinical outcomes of the disease. Additionally, it will significantly aid in identifying areas in which future research is needed., Competing Interests: Disclosures Peter L. Graversen: None Katra Hadji-Turdeghal: None Jacob Eifer Møller: Institutional research grant from Novo Nordic Foundation, Danish Hear Foundation and Abiomed outside submitted work. Unrelated to this study. Niels Eske Bruun: has received investigator initiated grants from: The Novo Nordisk Foundation, The Augustinus Foundation, The Kaj Hansen Foundation, and Health Insurance Denmark, unrelated to this study. Hicham Laghmoch: None Andreas Dalsgaard Jensen: None Jeppe K. Petersen: None Henning Bundgaard: has received lecture fees from Amgen, BMS, MSD and Sanofi, unrelated to this study. Kasper Iversen: None Jonas A Povlsen: None Claus Moser: has received an independent research grant from the Novo Nordisk Foundation in translational research grant number (NNF17OC0025074). Unrelated to this study. Morten Smerup: None Hanne Sortsøe Jensen: None Peter Søgaard: None Jannik Helweg-Larsen: None Daniel Faurholt-Jepsen: None Lauge Østergaard: has received an independent research grant from the Novo Nordisk Foundation (NNF23OC0081668) related to mitral valve regurgitation. Unrelated to this study. Lars Køber speakers fee from AstraZeneca, Baer, Boehringer, Novartis and Novo, unrelated to this study Emil L. Fosbøl: has received independent research grants related to valvular heart disease and endocarditis from the Novo Nordisk Foundation and the Danish Heart Association., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)