BACKGROUND: The epidemiological and clinical characteristics of infective endocarditis (IE) in mainland China, particularly following the COVID-19 pandemic, remain insufficiently understood. This study aims to examine temporal trends, clinical features, and factors influencing in-hospital mortality of IE in northern China from 2019 to 2023. METHODS: This multicenter, retrospective study included 961 patients diagnosed with IE between 2019 and 2023 across hospitals in Henan, Shandong, and Tianjin. Data were collected on demographics, comorbidities, COVID-19 status, and treatment modalities. Risk factors for in-hospital mortality were identified using logistic regression and Cox proportional hazards models. The effect of surgical intervention was assessed through propensity score matching. RESULTS: In-hospital mortality increased from 7.7% in 2019 to 26.4% in 2023, with an average annual growth of 38% (P = 0.008). The proportion of IE patients aged 65 years and older significantly increased, with this age group exhibiting the highest mortality rate (37.3%) by 2023. Surgical intervention was associated with a 91% reduction in in-hospital mortality (HR 0.09, 95% CI 0.05-0.15, P <
0.001). Independent risk factors for mortality included low left ventricular ejection fraction (LVEF), elevated heart rate (HR), cerebral hemorrhage, the use of vasoactive drugs and the requirement for continuous renal replacement therapy (CRRT). CONCLUSION: In-hospital mortality due to IE in northern China has risen substantially since 2019, particularly in elderly patients and those with comorbid conditions. There was no significant change in overall per capita hospitalization costs or length of stay. Surgical intervention significantly improved survival outcomes. Additionally, patients who have been infected with COVID-19 twice had an 81.3% increased risk of death. The results of this study provide important data into the epidemiological and medical burden of IE in mainland China since the COVID-19 epidemic.