Abstract Background Despite improvement in diagnostics and treatment options, infective endocarditis (IE) remains a significant burden for healthcare systems. While high-income countries have improved diagnosis of IE, the progress in interventional cardiology with a rise in cardiac devices associated infections, and people migrations offset some of these gains. Purpose To the best of our knowledge, there is a lack of comparative data between high-income countries, including the United States (US) and European Union (EU). Methods We collected the age-standardized rates of incidence (ASIR), deaths (ASDR), and disability-adjusted life years (ASDALYs) in the US and EU from 1993 to 2019 with the Global Health Data Exchange query tool. The Bayesian geospatial regression analysis and estimated annual percentage change (EAPC) to quantify the trends in age-standardized rates (ASR) were used. The data were stratified based on the gender, year, and location. Results Males in the US had an overall ASIR of 17.2/100k with an increasing trend between 1993 and 2019, and an annual average rate of change of 0.8 % (EAPC of 0.8%). A similar trend and higher rates were noted in males in the EU, with ASIR of 20.9/100k and EAPC of 2.0%. For the same period, females in the US had lower ASIR than females in the EU (11.9/100k vs. 13.6/100k) , and lower annual percent change (1% vs. 1.3%). In the US, ASDR was higher in males than females (1.6/100k vs. 1.28/100k), but females had higher annual percentage change (EAPC of 2.7% in males and 3.3% in females). Compared to US, males and females in the EU had lower ASDR in 2019 (1.2/100k in males, and 1.0/100k in females) with lower annual percentage changes of 2.5% and 1.7%, respectively. The ASDALY was significantly higher in the US, for both males (34.6/100k) and females (25.5/100k), with a greater increase in an annual average rate of change of 2.7% in females than in males (2.2%). EU males had ASDALY of 24.9/100k with an EAPC of 1.8%, while females had 16.7/100K with an annual average increase of 1.2%. Figure 1, Table 1 Conclusion ASIR of IE appears to be higher in the EU for both males and females. Conversely, ASDR and ASDALY manifest higher rates in the US across both genders, with females notably demonstrating a higher annual percentage increase for these metrics. Further studies are needed to assess the nature of these differences and to inform health policies.The age-standardized rates in US and EUThe differences in the EAPC