Background: The association of echocardiographic findings and subsequent risk of left-sided native valve endocarditis (LS-NVE) is undefined. The aim of this study was to determine if transthoracic echocardiographic (TTE) measurements are associated with the subsequent development of LS-NVE in patients without cardiac predisposing conditions. Methods: Institutional databases were evaluated for adults diagnosed with LS-NVE from 2008 to 2020. Patients with prosthetic valves, cardiovascular implantable electronic devices, intracardiac devices, injection drug use, and predisposing cardiac conditions were excluded. Only patients who had a TTE performed 6 months to 3 years before the development of LS-NVE were included as cases. Controls were patients within the same Mayo location with a TTE report and were matched in a 1:3 ratio according to age, gender, Charlson Comorbidity Index, and echocardiography date. Results: There were 148 cases and 431 matched controls. As compared to controls, IE cases had a higher prevalence of diabetes mellitus (46.6% vs. 30.4%) and chronic kidney disease (46.6% vs. 28.1%) (p<0.001). Left ventricular outflow tract velocity (p=0.017), left ventricular ejection fraction (p=0.018), and E: e’ ratio (p=0.050) were associated with LS-NVE. Conclusions: Echocardiographic measurements were associated with subsequent LS-NVE development in this pilot study. A larger cohort of LS-NVE patients, however, is needed to validate these findings.