The objective of this study was to analyze the difference in residual setup errors between 6D ExacTrac and 3D cone-beam computed tomography (CBCT) image-guided systems in spinal stereotactic body radiation therapy (SBRT). We investigated 76 patients with spinal tumors who received SBRT using Novalis Tx at our institution between January 2013 and September 2020. A Vac-lok (EZ-FIX®, Arlico Medical Company, South Korea) fixture and an assistive device, based on the region involved, were used to immobilize patients and to increase the inter-fractional setup reproducibility. The difference in the root mean square (RMS) between the 6D ExacTrac and 3D CBCT was -0.75 mm, 0.45 mm, 0.16 mm, and -0.03°; the RMS value was 1.31 mm, 1.06 mm, 0.87 mm, and 0.64°; and the standard deviation was 0.80 mm, 0.72 mm, 0.62 mm, and 0.44° for lateral, longitudinal, vertical, and yaw directions, respectively. The difference in the average RMS between ExacTrac and CBCT was <1.03 mm in the translation direction and <0.47° in the rotational direction; the results were statistically significant in the lateral, longitudinal, and vertical directions, but not in the yaw direction. Thus, it is necessary to verify the ExacTrac image according to the CBCT image.