Abstract Background Patients with Non-alcoholic fatty liver disease (NAFLD) hold an increased cardiovascular risk and present impaired markers of vascular, endothelial and myocardial function. Coenzyme Q10 (CQ10) is a powerful antioxidant that enhances mitochondrial function. Patients/methods: 52 patients (52±10 years old) with NAFLD were randomized to 240 mg CQ10 (n=25) or placebo (n=27). We measured at baseline and at six months post-treatment: i) Perfused boundary Region (PBR) of the sublingual arterial microvessels (Microscan, Glycocheck), ii) Carotid femoral pulse wave velocity - PWV (Complior ALAM), iii) Flow-mediated dilation (FMD) of the brachial artery, iv) Global left ventricular longitudinal strain (GLS) by speckle tracking imaging, v) Controlled attenuation parameter (CAP) measurement (FibroScan, Echosens). Results Six months post treatment with cQ10, values of PBR (2.12±0.19 vs. 2.28±0.23 μm), PWV (9.5±2.3 vs. 10.5±2.4m/s), CAP score (278.1±50, 2 vs. 305.3±44.5dB/m), FMD (6.61±4 vs. 5.02±2.6 %) and GLS (-19.3±1.9 vs -18.2±2 %) were improved (p<0.05 for all comparisons). On the contrary, the patients who were treated with placebo did not show statistically significant differences in PBR, PWV, CAP score, FMD and GLS after from 6 months (p>0.05). In the patients who received cQ10, the percentage reduction of CAP score at 6 months was directly proportional to the percent reduction in PWV (r=0.31, p=0.045) and inversely proportional to the percentage increase in FMD (r=-0.58, p=0.014). Conclusion Six-month treatment with CoQ10 reduces liver steatosis in patients with NAFLD. CoQ10 is associated with improved endothelial, vascular and LV myocardial function in patients with NAFLD.