Despite the association of a worse HF-related clinical status with lower CoQ10 levels, the prognostic use of CoQ10 is controversial. The aim of this study is to optimize pharmacotherapy for patients with ischaemic CHF, based on the clinical and functional parameters of the heart and brain natriuretic peptide (BNP) plasma levels, which are correlated with the CoQ10 plasma levels, and to assess patient prognosis after receiving CoQ10 therapy. This prospective clinical study included 75 patients aged 56 to 63 years old with coronary heart disease (CHD) classified as class I–III according to the NYHA classification. After assessment of the clinical-instrumental characteristics of the CVD course (complaints, medical history, physical examination, a 6-minute walk test, echocardiography, and test for reactive hyperaemia), we determined the BNP level and CoQ10 plasma levels. At the same time, we assessed the efficacy of CoQ10 treatment (at a dose of 60 mg/per day) and tolerability in CVD-combined therapy during a follow-up of 12 weeks. CoQ10 supplementation in HF patients induced improvements in their functional cardiac parameters, such as the ejection fraction. Our results suggest that supplemental CoQ10 may be a useful option for effective management of heart failure and warrant future adequately powered randomized controlled trials of CoQ10 supplementation in patients with HF. © 2018, University of Kragujevac, Faculty of Science. All rights reserved.