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Background: Infective endocarditis (IE), a severe and economically impactful condition, lacks substantial epidemiological data in the North Africa and Middle East (NAME) region. This study focused on analyzing the trends and burden of IE in NAME from 1990 to 2019, taking into account factors like age, gender, and socio-demographic index (SDI). Methods: The Global Burden of Disease data from 1990 to 2019 was retrieved from the Institute for Health Metrics and Evaluation (IHME) website. Results: Between 1990 and 2019, the age-standardized rates (ASR) for IE incidence increased by 59%, and prevalence and years lived with disability (YLDs) rose by 12% and 9%, respectively, while the ASRs for deaths, disability-adjusted life years (DALYs), and years of life lost (YLLs) saw reductions of 22%, 34%, and 34% in the NAME region. Death rates among children under five declined by 72%. Gender and the SDI did not significantly influence these changes. Saudi Arabia witnessed the most significant increase in ASR of IE incidence since 1990, while Turkey had the highest rates in 2019. The year 2019 also saw the highest death rate among those aged 70 and over, with over 91 000 DALYs from IE. DALYs decreased by 71.5% for children under five from 1990 to 2019 but remained stable for individuals in their seventies. Jordan showed the most notable decrease in ASRs for deaths, DALYs, and YLLs among children under five. Conclusion: This study highlights the changing epidemiology of IE in the NAME region, recommending the establishment of multidisciplinary IE registries, antibiotic prophylaxis guidelines for healthcare-associated IE, and strategies to control antimicrobial resistance as key mitigation measures. [ABSTRACT FROM AUTHOR]