Abstract Background Infective endocarditis (IE) occurs worldwide and is associated with high mortality. Diagnosis and management of IE requires timely transesophageal echocardiography (TEE), which may not be consistently available in many institutions, especially on weekends. Hence, we wanted to evaluate the effect of weekend admission on IE in-hospital outcomes. Purpose To evaluate the differences in mortality and TEE utilization between weekend and weekday admissions in IE hospitalizations. Methods In this retrospective cohort study, we queried the 2017 and 2018 National Inpatient Sample (NIS) database to identify primary diagnosis of IE using appropriate ICD-10 CM codes. The variable for weekend admission which is available in the dataset was used to categorize hospitalizations into weekend and weekday admission groups. TEE procedures were identified using appropriate ICD-10 PCS codes. We used the Chi-square test to evaluate the difference between binary variables, and Student's t- test for differences between continuous variables. Multivariate logistic regression analysis was used to adjust for potential hospital and patient level confounders (age, sex, race, diabetes, hypertension, obesity, acute renal failure, diabetes, and Elixhauser comorbidity index score). Stata SE 16.1 was used to perform all statistical analyses. Results Among the identified 27,735 weighted adult IE hospitalizations, 6,145 (22.1%) were admitted on weekends. Weekend IE admissions were similar to weekday in all measured aspects except for elective admissions (Table 1). There were more elective admissions on the weekday compared to the weekend (11.3% for weekday vs. 4.9% for weekend; p<0.01). The mean age was 51 years for both hospitalizations. There were more TEEs in the first 24 hrs in weekday compared to weekend hospitalizations (7.8% vs. 3.4%; p<0.01). After adjusting for potential patient and hospital level confounders, there was no difference in mortality [Adjusted Odds ratio (aOR): 0.91 (0.62–1.33); p=0.63)], valve replacement procedures [aOR: 0.91 (0.62–1.33); p=0.63)] or incidence of atrioventricular (AV) blocks [aOR: 0.91 (0.62–1.33); p=0.63)] comparing weekend versus weekday IE hospitalizations. Additionally, we did not observe any mean difference in length of stay and total hospitalization charges between weekend and weekday hospitalizations. Conclusion In patients with IE, weekend admissions did not have a clinically significant difference in mortality, length of stay, incidence of AV blocks or valve replacements compared to weekday admissions. TEEs were performed equally in IE hospitalizations regardless of day of admission; however, early TEEs (within 24 hours of admission) were more commonly associated with weekday admission. Despite this, there was no clinically significant difference in the mortality between early TEEs and TEEs done after 24 hours of admission. Funding Acknowledgement Type of funding sources: None.