This study evaluates the diagnostic performance of the 2023 Duke-International Society of Cardiovascular Infectious Diseases (ISCVID) criteria for infective endocarditis (IE) compared to previous versions from 2000 (Duke-Ii 2000) and 2015 (Duke-ESC 2015). The study was conducted at two university hospitals in Switzerland between 2014 and 2022, involving 2132 episodes with suspected IE. The final diagnosis of IE was made by the Endocarditis Team based on pathological, surgical, and microbiological data. The 2023 Duke-ISCVID criteria showed higher sensitivity (84%) compared to previous versions (70%), but lower specificity (60%) compared to previous versions (74%). The study highlights the increased sensitivity of the new criteria but also suggests the need for further research to balance sensitivity and specificity without compromising diagnostic accuracy. Key changes in the 2023 criteria include the addition of cardiac CT and 18F-FDG PET/CT for both native and prosthetic valve IE, and the inclusion of intraoperative evidence as a major criterion. The study also emphasizes the importance of 18F-FDG PET/CT in diagnosing IE in patients with prosthetic valves or cardiac implantable electronic device (CIED) leads, where echocardiography may be inconclusive.This study evaluates the diagnostic performance of the 2023 Duke-International Society of Cardiovascular Infectious Diseases (ISCVID) criteria for infective endocarditis (IE) compared to previous versions from 2000 (Duke-Ii 2000) and 2015 (Duke-ESC 2015). The study was conducted at two university hospitals in Switzerland between 2014 and 2022, involving 2132 episodes with suspected IE. The final diagnosis of IE was made by the Endocarditis Team based on pathological, surgical, and microbiological data. The 2023 Duke-ISCVID criteria showed higher sensitivity (84%) compared to previous versions (70%), but lower specificity (60%) compared to previous versions (74%). The study highlights the increased sensitivity of the new criteria but also suggests the need for further research to balance sensitivity and specificity without compromising diagnostic accuracy. Key changes in the 2023 criteria include the addition of cardiac CT and 18F-FDG PET/CT for both native and prosthetic valve IE, and the inclusion of intraoperative evidence as a major criterion. The study also emphasizes the importance of 18F-FDG PET/CT in diagnosing IE in patients with prosthetic valves or cardiac implantable electronic device (CIED) leads, where echocardiography may be inconclusive.