Optimisation of imaging modes for kilovoltage CT (kVCT) used for treatment planning and megavoltage CT (MVCT) image guidance used in ungated helical tomotherapy was investigated for laterally moving targets. Computed tomography images of the QUASAR™ Respiratory Motion Phantom were acquired without target motion and for lateral motion of the target, with 2-cm peak-to-peak amplitude and a period of 4 s. Reference kVCT images were obtained using a 16-slice CT scanner in standard fast helical CT mode, untagged average CT mode and various post-processed 4D-CT modes (0% phase, average and maximum intensity projection). Three sets of MVCT images with different inter-slice spacings of were obtained on a Hi-Art tomotherapy system with the phantom displaced by a known offset position. Eight radiation therapists performed co-registration of MVCT obtained with 2-, 4- and 6-mm slice spacing and kVCT studies independently for all 15 CT imaging combinations. In the investigated case, the untagged average kVCT and 4-mm slice spacing for the MVCT yielded more accurate registration in the transverse plane. The average residual uncertainty of this combination of imaging procedures was 0.61 ± 0.16 mm in the longitudinal direction, 0.45 ± 0.14 mm in the anterior–posterior direction and insignificant in the lateral direction. Manual registration of MVCT–kVCT study pairs is necessary to account for a target in significant lateral motion with respect to bony structures.