Introduction: Multiple sclerosis (MS), debilitating disease involving primarily the central nervous system, represents the main cause of nontraumatic neurological invalidity in young adults. Involvement of the autonomous nervous system and the assumed autoimmune etiology may lead to cardiovascular dysfunction. Aim: To assess systolic left and right ventricular function and vascular function in newly diagnosed patients with MS with no immunomodulatory treatment, by comparison with treated MS, and with controls (matched for age, sex and risk factors). Methods: 90 subjects (35 ± 10 years, 59 women) were studied: 30 patients with newly diagnosed MS (MS1); 30 patients with treated MS (MS2); and 30 control subjects (C). LV systolic function was assessed by 2D EF, 3D EF, 3D global longitudinal strain (3DGLS), 6 basal segments averaged systolic velocity (S\’), and global longitudinal strain (GLS) by speckle tracking. RV systolic function was assessed by fractional area shortening (FAS), tricuspid annular systolic excursion (TAPSE), RV myocardial performance index (RVMPI), RV global strain (RVGS) by speckle tracking and systolic pulmonary artery pressure (SPAP). Arterial remodeling and stiff ness were assessed by intima media-thickness, pulse wave velocity and parameters of wave intensity; endothelial function by fl ow mediated dilation. Results: Patients with MS had signifi cantly aff ected LV [2DEF (%) MS1= 55 ± 6, MS2 = 56 ± 5, C = 66 ± 6, 3DEF (%) MS1= 53 ± 7, MS2 = 52 ± 6,C = 64 ± 2, S\ (cm/s) MS1= 5.9 ± 1.1, MS2 = 6.0 ± 1.2,C = 7.3 ± 0.9, GLS (%) MS1= -19.5 ± 2.6, MS2 = -20.2 ± 1.8, C = -22.6 ± 1.8, 3DGLS (%) MS1= -14.7 ± 3.1, MS2 = -13.3 ± 1.5, C = -20.3 ± 1.8 [and RV [FAC (%) MS1 = 40.7 ± 7.9, MS2 = 44.6 ± 6.7, C = 53.1 ± 8.9, TAPSE (mm) MS1 = 22.7 ± 2.2, MS2 = 23.0 ± 2.5, C = 26.3 ± 2.7, RVMPI MS1= 0.6 ± 0.1, MS2 = 0.6 ± 0.1,C = 0.4 ± 0.1, RVGS (%) MS1 = -22.1 ± 3.5, MS2 = -22.8 ± 3.1, C = -25.8 ± 4.0, SPAP (mm Hg) MS1= 22 ± 8, MS2 = 27 ± 12, C =15 ± 6] systolic function by comparison to controls, demonstrated by 2D and 3D echocardiography, with no diff erences between the 2 MS groups (MS1 vs. C: all p < 0.001; MS2 vs. C: all p < 0.001) (table). All parameters of arterial and endothelial function were similar. Conclusions: Patients with MS, either treated or not, have subclinical biventricular systolic dysfunction with normal vascular function, suggesting an intrinsic myo cardial impairment, probably mediated through neuronal impairment. Early diagnosis by 2D and 3D echocardiography might be important for initiating preventive actions.