The authors compared 12 pairs of cerebral [18F]-fluoro-deoxyglucose (FDG) 2D/3D image sets from a GE/Advance PET scanner, incorporating the actual corrections used on human subjects. Differences in resolution consistent with other published values were found. There is a significant difference in axial resolution between 2D and 3D, and the authors focused on this as it is a scanner feature that cannot be readily changed. Previously published values for spatial axial resolution in 2D and 3D modes were used to model the differential axial smoothing at each image voxel. This model was applied to the 2D FDG images, and the resulting smoothed data indicate the published differences in axial resolution between 2D and 3D modes can account for 30-40% of the differences between these image sets. The authors then investigated the effect this difference might have on analysis typically performed on human FDG data. A phantom containing spherical hot- and cool-spots in a warm background to mimic a typical human cerebral FDG PET scan was scanned for a variety of time durations (30, 15, 5, 1 min). Only for the 1-minute frame (total counts 2D:6M, 3D:30M) is there an advantage to using 3D mode; for the longer frames which are more typical of a human FDG protocol, the reliability for extracting regions-of-interest is the same for either mode while 2D mode shows better quantitative accuracy