<p>Due to the high mortality and morbidity of patients with aortic and mitral endocarditis, careful monitoring is necessary to recognize an early failure of antibiotic and cardiokinetic therapy and avoid a possible cardiogenic or septic shock. The timing of surgery is crucial for patients in whom medical therapy fails. The aim of our study is to identify potential echocardiographic biomarkers of adverse events in patients with left-sided native valve infective endocarditis. Sixty-four patients with aortic and/or mitral valve dysfunction(AOVD, MVD) from infective endocarditis were studied by three-dimensional transesophageal echocardiography(3DTEE) and transthoracic speckle tracking echocardiography(3DSTE). Sixty-four healthy subjects were selected as controls. Vegetation size and valvular features were assessed by 3DTEE. Standard transthoracic echocardiographic parameters were determined. Global left ventricular(LV) longitudinal strain(3D-LVGLS) and area strain(3D-LVGAS) were measured by 3DSTE. Averaged LV rotation and rotational velocities from the base and apex were obtained and used for calculation of LV twist and torsion. Endpoints were embolism and in-hospital mortality. Maximal vegetation dimension was 10&#xa0;(4-29) mm if measured by 3DTEE and 7&#xa0;(4-20) mm if measured by 2DTEE (<i>p</i> = 0.02). Valvular and perivalvular complications were present in 21(33%) and 13(20%) patients. AOVD/MVD patients had decreased GLS (<i>p</i> = 0.011), GAS (<i>p</i> = 0.003) and LVtwist (<i>p</i> = 0.024) compared with control subjects. By multivariate analysis, vegetation mobility(<i>p</i> = 0.001), vegetation size(<i>p</i> = 0.003), perivalvular complications(<i>p</i> = 0.006), and bivalvular vegetations(<i>p</i> = 0.009) were independent predictors of embolic events. Valve-related complications(<i>p</i> = 0.001), vegetation size(<i>p</i> = 0.029), 3D-LVGLS(<i>p</i> = 0.013), and 3D-LVGAS(<i>p</i> = 0.002) were predictive of in-hospital mortality. Using a composite endpoint of both outcomes, ROC curves suggested that 3D valvular and LV function parameters had higher diagnostic accuracy for identifying adverse events than 2D parameters. 3D combined evaluation of vegetation size, regurgitant volume and LV area strain had the highest diagnostic accuracy (AUC 0.89, <i>p</i> = 0.001). Significant improvement in global χ² value was noted with 3D strain parameters compared with LV ejection fraction for predicting outcome (from 82.3 to 90.5, <i>p</i> = 0.004). 3D combined assessment of anatomical-functional valve characteristics and LV function strain parameters improves the sensitivity of the echocardiographic indices in predicting cardiac morbidity and mortality of left-sided native valve infective endocarditis.</p> Graphical Abstract <p></p>