PURPOSE: To assess whether isotropic resolution is attainable in three-dimensional craniocervical helical computed tomography (CT). MATERIALS AND METHODS: Two cadaveric cervical spine and two orbital phantoms were scanned in air and water by using 180 degrees-interpolated helical CT with three-dimensional reconstruction. Scan parameters yielded nominally isotropic voxels with reconstruction of 1-mm collimated and incremental sections at 0.2-mm intervals. CT scan angle was varied with the assumption that volume-averaging artifacts should be scan angle-independent with isotropic voxels. Twelve blinded observers analyzed three-dimensional images generated from multiple CT orientations to assess changes in volume-averaging artifacts that would indicate voxel anisotropy. RESULTS: Significant observable differences in three-dimensional image representation were present in test anatomic regions in one cervical spine phantom (two-tailed P < .006) and in both orbital phantoms (P < .008 and P < .006). No statistically significant differences were present for control anatomic regions. CONCLUSION: Isotropic scanning is not possible in three-dimensional craniocervical helical CT.