Objective Changes of energy metabolism in the failing human heart could further exacerbate functional deterioration. Our aim is to evaluate the nature of the abnormalities of myocardial energy metabolism in the human heart at end stage heart failure due to hypertrophic or dilated cardiomyopathy.Methods Left ventricle cardiac specimens from patients undergoing heart transplantation with dilated cardiomyopathy (DCM n = 14) or hypertrophic cardiomyopathy (HCM n = 5) and samples obtained from non diseased donor hearts (C n = 4) were analyzed by HPLC for phosphocreatine (PCr), creatine (Cr), adenine nucleotides with their breakdown products and guanine nucleotides. Results are expressed in μmoles/g wet weight as the mean ± SEM.Results Total creatine levels (phosphocreatine + creatine) (3.87 ± 0.57 * and 5.09 ± 1.23 * in the DCM and HCM patients compared to C 10.73 ± 3.46) * p < 0.05, were significantly decreased in the two groups of diseased hearts. However, no significant differences were seen in total adenine nucleotides (3.45 ± 0.38 for DCM, 4.22 ± 0.72 for HCM compared to 3.17 ± 0.45 in C), total catabolites (hypoxanthine, inosine and adenosine) (3.56 ± 0.38 for DCM, 4.67 ± 0.81 for HCM compared to 4.11 ± 1.02 in C), total guanine nucleotides (0.32 ± 0.04 for DCM, 0.31 ± 0.05 for HCM vs C 0.26 ± 0.03 and total NAD (NAD + ADPR) (0.32 ± 0.03 for DCM, 0.46 ± 0.08 for HCM vs C 0.38 ± 0.03).Conclusions Human heart failure is associated with decreased energy reserves and altered intracellular energy transfer due to depletion of the myocardial creatine pool.