Objective. To study the effect of Mexidol on the functional state of myocardium, NT-proBNP level, exercise tolerance, quality of life, severity of oxidative stress, inflammatory response and endothelial dysfunction in patients with chronic brain ischemia and chronic heart failure NYHA class II-III in a 13-week sequential (intravenous and oral) therapy with Mexidol® and standard therapy. Material and methods. The study included 44 patients with chronic brain ischemia and chronic heart failure NYHA class II-III. Mean age was 65.5±11.8 years, men accounted 75%. The group of Mexidol + standard therapy of chronic heart failure included 21 patients, the group of standard therapy - 23 patients. Echocardiography parameters, exercise tolerance test (six minute walk test, SMWT), patient’s clinical condition according to SHOKS scale (modification by V. Yu. Mareev), NT-proBNP concentration, markers of oxidative stress (malonic dialdehyde (MDA), superoxide dismutase (SOD)), inflammatory reaction (C-reactive protein (CRP), tumor necrosis factor a (TNFα)), homocysteine and cystatin C were examined initially, after 7 days and 13 weeks. The quality of life was assessed initially and at the end of the study using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). Results. «Mexidol + standard therapy» group was characterized by more significant improvement in the quality of life, better SMWT data and SHOKS scores, significant decrease in end-diastolic and end-systolic LV dimensions, as well as NT-proBNP level after 7 days and 13 weeks compared to the basic therapy group. Mexidol administration reduced MDA concentration and increased SOD activity after 7 days and 13 weeks. We also observed a significant decrease in CRP and TNFα levels after 7 days and 13 weeks in the same group. Less augmentation of homocysteine was revealed in the Mexidol therapy group. There were no significant between-group differences in cystatin C levels. Conclusion. Mexidol in addition to standard therapy of chronic brain ischemia and chronic heart failure class II-III has a favorable effect on the quality of life, functional status, improves clinical condition and intracardiac circulation, decreases concentration of NT-proBNP, promotes antioxidant activity, reduces inflammatory reaction, slows down increase of homocysteine and does not influence kidney function. © 2021, Media Sphera Publishing Group. All rights reserved.