PURPOSE: Infective endocarditis (IE) is a evolving disease with a shifting epidemiology and disease burden over time. This study aimed to compare the epidemiological and clinical aspects of IE over three time periods across eleven years. METHODS: This was a retrospective cohort, multicenter study conducted in Türkiye, comparing three periods: 2013-2016, 2017-2020, and 2021-2023. Epidemiological and microbiological characteristics, as well as patient outcomes, were analyzed and compared across these periods. RESULTS: A total of 1,044 patients diagnosed with IE were included. The median (Q1-Q3) age was 57 (44-68) years, with an increasing pattern (p <
0.001). Throughout the study period, the prevalence of intracardiac devices increased, whereas the prevalence of degenerative and congenital heart diseases declined. Among all patients, the most frequently identified pathogens were staphylococci (36.4%), followed by streptococci (14.0%) and enterococci (11.9%). Throughout the three periods, there was a significant increase in staphylococci, with S. aureus emerging as the predominant pathogen in all type IE. The in-hospital mortality rate among all patients was 22.5%. Independent risk factors for in-hospital mortality included ≥ 65 age(OR = 1.9), chronic kidney disease (OR = 1.9), nosocomial acquisition (OR = 2.1), Candida spp. infection (OR = 2.9), prosthetic valve IE (OR = 1.9), vegetation size >
15 mm (OR = 1.6), and central nervous system emboli (OR = 2). CONCLUSION: The epidemiology of IE is undergoing significant changes, leading to shifts in microbiological profiles and clinical presentations. Effective management of IE should be guided by established clinical guidelines while integrating up-to-date epidemiological data to ensure comprehensive and evidence-based patient care.