Methods of measuring uncertainties in rigid body image registration of fan beam computed tomography (FBCT) to cone beam CT (CBCT) have been developed for automatic image registration algorithms in a commercial image guidance system (Synergy, Elekta, UK). The relationships between image registration uncertainty and both imaging dose and image resolution have been investigated with an anthropomorphic skull phantom and further measurements performed with patient images of the head. A new metric of target registration error is proposed. The metric calculates the mean distance traversed by a set of equi-spaced points on the surface of a 5 cm sphere, centred at the isocentre when transformed by the residual error of registration. Studies aimed at giving practical guidance on the use of the Synergy automated image registration, including choice of algorithm and use of the Clipbox are reported. The chamfer-matching algorithm was found to be highly robust to the increased noise induced by low-dose acquisitions. This would allow the imaging dose to be reduced from the current clinical norm of 2 mGy to 0.2 mGy without a clinically significant loss of accuracy. A study of the effect of FBCT slice thickness/spacing and CBCT voxel size showed that 2.5 mm and 1 mm, respectively, gave acceptable image registration performance. Registration failures were highly infrequent if the misalignment was typical of normal clinical set-up errors and these were easily identified. The standard deviation of translational registration errors, measured with patient images, was 0.5 mm on the surface of a 5 cm sphere centred on the treatment centre. The chamfer algorithm is suitable for routine clinical use with minimal need for close inspection of image misalignment.