Purpose: Historically, the process of positioning a patient prior to imaging verification used a set of permanent patient marks, or tattoos, placed subcutaneously. After aligning to these tattoos, plan specific shifts are applied and the position is verified with imaging, such as cone-beam computed tomography (CBCT). Due to a variety of factors, these marks may deviate from the desired position or it may be hard to align the patient to these marks. Surface-based imaging systems are an alternative method of verifying initial positioning with the entire skin surface instead of tattoos. The aim of this study was to retrospectively compare the CBCT-based 3D corrections of patients initially positioned with tattoos against those positioned with the C-RAD CatalystHD surface imager system. Methods: A total of 6000 individual fractions (600-900 per site per method) were randomly selected and the post-CBCT 3D corrections were calculated and recorded. For both positioning methods, four common treatment site combinations were evaluated: pelvis/lower extremities, abdomen, chest/upper extremities, and breast. Statistical differences were evaluated using a paired sample Wilcoxon signed-rank test with significance level of <0.01. Results: The average magnitudes of the 3D shift vectors for tattoos were 0.9 ± 0.4 cm, 1.0 ± 0.5 cm, 0.9 ± 0.6 cm and 1.4 ± 0.7 cm for the pelvis/lower extremities, abdomen, chest/upper extremities and breast, respectively. For the CatalystHD, the average magnitude of the 3D shifts for the pelvis/lower extremities, abdomen, chest/upper extremities and breast were 0.6 ± 0.3 cm, 0.5 ± 0.3 cm, 0.5 ± 0.3 cm and 0.6 ± 0.2 cm, respectively. Statistically significant differences (P < 0.01) in the 3D shift vectors were found for all four sites. Conclusion: This study shows that the overall 3D shift corrections for patients initially aligned with the C-RAD CatalystHD were significantly smaller than those aligned with subcutaneous tattoos. Surface imaging systems can be considered a viable option for initial patient setup and may be preferable to permanent marks for specific clinics and patients.