PET radiopharmaceuticals can non-invasively measure free fatty acid (FFA) tissue uptake. Investigators often use PET scan-derived data to calculate FFA flux. We tested whether the [1-¹¹C]palmitate PET measures of palmitate flux provide results equivalent to a continuous infusion of [U-¹³C]palmitate. Nine volunteers participated in study 1 to evaluate whether a rapidly (10-20 seconds) given bolus of [1-¹¹C]palmitate affects calculated flux results. Thirty volunteers participated in study 2, which was identical to study 1 except that the [1-¹¹C]palmitate bolus was given over 1 minute. Volunteers in both studies also received a continuous intravenous infusion of [U-¹³C]palmitate. Plasma palmitate concentrations and enrichment were measured by liquid chromatography/mass spectrometry. The PET/CT images were analyzed on a workstation running PMOD. Palmitate flux was estimated using PET time activity curve (TAC) data from regions of interest in the left ventricle (LV) and aorta, both with and without hybrid TACs that employed the ¹¹CO₂-corrected data for the first 5 min and the ¹¹CO₂-corrected blood radioactivity for the remainder of the PET scan. Palmitate flux in study 1 measured with PET [1-¹¹C]palmitate and [U-¹³C]palmitate were not correlated and the PET [1-¹¹C]palmitate flux was significantly less than the [U-¹³C]palmitate measured flux. In study 2 the palmitate flux using PET [1-¹¹C]palmitate hybrid LV models provided closer mean estimates of [U-¹³C]palmitate measured flux. The best PET calculation approaches predicted 64% of the inter-individual variance in [U-¹³C]palmitate measured flux. Palmitate kinetics measured using [1-¹¹C]palmitate/PET do not provide the same palmitate kinetic results as the continuous infusion [U-¹³C]palmitate approach.