Infective endocarditis (IE) is a life threatening disease requiring lengthy hospitalizations, complex multidisciplinary management and high health care costs. In this study, we analyzed the National Readmissions’ Database (NRD) to identify infective endocarditis cases and the causative organisms, clinical determinants, length of stay, in-hospital mortality, and 30-day hospital readmission rates. The study cohort was derived from Healthcare Cost and Utilization Project’s National Readmission Database between 2010-15. We queried the National Readmissions’ Database using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic code for infective endocarditis (421.0) and identified a total of 187,438 index admissions. SAS 9.4 (SAS Institute Inc., Cary, NC) was utilized for statistical analyses. A total of 187,438 patients with a primary diagnosis of IE were identified over 6 years (2010-2015). Twenty-four percent (44,151 patients) were readmitted within 30 days. Most common etiologies for readmission included sepsis (14%), acute heart failure (8%), acute kidney injury (6%), intracardiac device infection (5.6%) and recurrence of IE (2.7%). Predictors of increased readmissions included female sex, staphylococcus aureus infection, diabetes, chronic lung disease, chronic liver disease, acute kidney injury, acute heart failure and anemia. In-hospital mortality for the readmission of IE was 13%, and average length of stay during the re-admission was 12 days. IE is associated with high rates of index admission mortality and for 30-day readmissions of which are associated with a substantial risk of death.