Using a novel positron emission tomography (PET) method with oral administration of 14(R,S)-[¹⁸F]-fluoro-6-thia-heptadecanoic acid (¹⁸FTHA), we recently demonstrated that subjects with impaired glucose tolerance (IGT) display an impairment in cardiac function associated with increased myocardial uptake of dietary fatty acids. Here, we determined whether modest weight loss induced by lifestyle changes might improve these cardiac metabolic and functional abnormalities. Nine participants with IGT, enrolled in a one-year lifestyle intervention trial, were invited to undergo determination of organ-specific postprandial dietary fatty acids partition using the oral ¹⁸FTHA method, and cardiac function and oxidative metabolic index using PET 11C-acetate kinetics with ECG-gated PET ventriculography prior to and after the intervention. The intervention resulted in significant weight loss and reduction of waist circumference, without significant change in postprandial plasma glucose, insulin, nonesterified fatty acid or triglyceride levels. We observed a significant increase in stroke volume, cardiac output and left ventricular ejection fraction associated with reduced myocardial oxidative metabolic index and fractional dietary fatty acid uptake. Modest weight loss corrects the exaggerated myocardial channelling of dietary fatty acids and improves myocardial energy substrate metabolism and function in IGT subjects (ClinicalTrial.gov NCT 00969007).