To investigate the frequency, magnitude and possible causes of frame-shifts that may occur between treatment planning and treatment delivery when performing Gamma Knife radiosurgery with rigid frame-based immobilization. Differences between computed tomography (CT) framed fiducial stereotactic coordinate reference and cone beam computed tomography stereotactic coordinates after image registration were recorded for 49 frame-based GK radiosurgery cases performed using the Gamma Knife Icon. Parameters recorded include rotational shifts, translational shifts, and the GK-computed Maximum Shot Displacement (MSD) between the two stereotactic coordinate spaces. Other patient-specific parameters were collected and linear regression analysis was performed to evaluate predictors of increased displacement. The median values of rotational shifts were: pitch 0.14°, yaw 0.17°, and roll 0.13°. The median absolute values of translational shifts were: left-right 0.39mm, anteroposterior 0.14mm, and superior-inferior 0. 22mm. The median value of MSD was 0.71mm. Twelve cases (24.5%) had a MSD of greater than 1.0mm. Male gender was associated with increased MSD (p = 0.013) and translational shifts (root-mean-squared value, p = 0.017). Cases with large differences between right and left sided pin lengths were also associated with increased MSD (p = 0.011). The use of CBCT image guidance in frame-based GK radiosurgery allows unintended frame shifts to be identified and corrected. A significant fraction (24.5%) of patients had large enough shifts to result in a MSD of greater than 1.0mm. Male gender and eccentrically placed frames were associated with increased MSD, and particular care should be taken in these cases.