Objective.Contrast recovery coefficient (CRC) is essential for image quality (IQ) assessment in positron emission tomography (PET), typically measured according to the National Electrical Manufacturers Association (NEMA) NU 2 standard. This study quantifies systematic uncertainties of the CRC measurement by a numerical investigation of the effects from scanner-independent parameters like voxel size, region-of-interest (ROI) misplacement, and sphere position on the underlying image grid.Approach.CRC measurements with 2D and 3D ROIs were performed on computer-generated images of a NEMA IQ-like phantom, using voxel sizes of 1-4 mm for sphere diameters of 5-40 mm-first in absence of noise and blurring, then with simulated spatial resolution and image noise with varying noise levels. The systematic uncertainties of the CRC measurement were quantified from above variations of scanner-independent parameters. Subsampled experimental images of a NEMA IQ phantom were additionally used to investigate the impact of ROI misplacement at different noise levels.Main results.In absence of noise and blurring, systematic uncertainties were up to 28.8% and 31.0% with 2D and 3D ROIs, respectively, for the 10 mm sphere, with the highest impact from ROI misplacement. In all cases, smaller spheres showed higher uncertainties with larger voxels. Contrary to prior assumptions, the use of 3D ROIs did not exhibit less susceptibility for parameter changes. Experimental and computer-generated images both demonstrated considerable variations on individual CRC measurements when background coefficient-of-variation exceeded 20%, despite negligible effects on mean CRC.Significance.This study underscores the effect of scanner-independent parameters on reliability, reproducibility, and comparability of CRC measurements. Our findings highlight the trade-off between the benefits of smaller voxel sizes and noise-induced CRC fluctuations, which is not considered in the current version of the NEMA IQ standards. The results furthermore warrant adjustments to the standard to accommodate the advances in sensitivity and spatial resolution of current-generation PET scanners.