OBJECTIVES. The purpose of this study was to determine whether patients with idiopathic dilated cardiomyopathy (IDCM) exhibit alterations in myocardial fatty acid and glucose metabolism. BACKGROUND. Alterations in myocardial metabolism have been implicated in the pathogenesis of heart failure (HF); however, studies of myocardial metabolic function in human HF have yielded conflicting results. Animal models of HF have shown a downregulation of the expression of enzymes of fatty acid beta-oxidation that recapitulates the fetal energy metabolic program, in which fatty acid metabolism is decreased and glucose metabolism is increased. METHODS. Seven patients with IDCM (mean left ventricular ejection fraction 27 ± 8%) and 12 normal controls underwent positron emission tomography for measurements of myocardial blood flow (MBF), myocardial oxygen consumption (MVO2), myocardial glucose utilization (MGU), myocardial fatty acid utilization (MFAU) and myocardial fatty acid oxidation (MFAO). RESULTS. The systolic and diastolic blood pressures, plasma substrates and insulin levels, MBF and MVO2, were similar between groups. The rates of MFAU and MFAO were significantly lower in IDCM than in the normal control group (MFAU: 134 ± 44 vs. 213 ± 49 nmol/g/min, p = 0.003; and MFAO: 113 ± 50 vs. 205 ± 49 nmol/g/min, p = 0.001) and the rates of MGU were significantly higher in IDCM than the normal control group (MGU: 247 ± 63 vs. 125 ± 64 nmol/g/min, p < 0.001). CONCLUSIONS. Patients with IDCM exhibit alterations in myocardial metabolism characterized by decreased fatty acid metabolism and increased myocardial glucose metabolism, a pattern similar to that shown in animal models of HF. Whether alterations in myocardial metabolism constitute an adaptive response or mediate the development of HF remains to be determined.