Recent advances in versatile automated gauging have enabled accurate geometric tolerance assessment on the shop floor. This paper is concerned with the uncertainty evaluation associated with comparative coordinate measurement using the design of experiments (DOE) approach. It employs the Renishaw Equator which is a software-driven comparative gauge based on the traditional comparison of production parts to a reference master part. The fixturing requirement of each production part to the master part is approximately ±1mm for a comparison process with an uncertainty of ±2μm. Therefore, a number of experimental designs are applied with the main focus on the influence of part misalignment from rotation between master and measure coordinate frames on the comparator measurement uncertainty. Other factors considered include measurement mode mainly in scanning and touch-trigger probing (TTP) and alignment procedure used to establish the coordinate reference frame (CRF) with respect to the number of contact points used for each geometric feature measured. The measurement uncertainty analysis of the comparator technique used by the Equator gauge commences with a simple measurement task using a gauge block to evaluate the three-dimensional (3D) uncertainty of length comparative coordinate measurement influenced by an offset by tilt in one direction (two-dimensional angular misalignment). Then, a specific manufactured measurement object is employed so that the comparator measurement uncertainty can be assessed for numerous measurement tasks within a satisfactory range of the working volume of the versatile gauge. Furthermore, in the second case study, different types of part misalignment including both 2D and 3D angular misalignments are applied. The time required for managing the re-mastering process is also examined. A task specific uncertainty evaluation is completed using DOE. Also, investigating the effects of process variations that might be experienced by such a device in workshop environments. It is shown that the comparator measurement uncertainties obtained by all the experiments agree with system features under specified conditions. It is also demonstrated that when the specified conditions are exceeded, the comparator measurement uncertainty is associated with the measurement task, the measurement strategy used, the feature size, and the magnitude and direction of offset angles in relation to the reference axes of the machine. In particular, departures from the specified part fixturing requirement of Equator have a more significant effect on the uncertainty of length measurement in comparator mode and a less significant effect on the diameter measurement uncertainty for the specific Equator and test conditions.