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BACKGROUND On a new dedicated radiosurgery unit enabling frameless treatments, a cone-beam computed tomography (CBCT) can be used for stereotactic definition. Since magnetic resonance imaging (MRI) is used to delineate target, reproducible MRI-to-CBCT coregistration is vital for accurate target localization. OBJECTIVE To evaluate reproducibility of image coregistration in patient images. METHODS Three types of coregistration (source-to-target) were analyzed: (1) MRI-to-CT; (2) MRI-to-CBCT; and (3) CT-to-CBCT. For each patient (n = 15), each coregistration type was independently performed 5 to 30 times (total: 465 coregistrations). Each coregistration yielded a transformation matrix, which was subsequently applied to transform every point in the source image to stereotactic coordinates. Two metrics were measured: (1) target registration error (TRE): mean distance between the registered position of each target point and the average registration position of that point; (2) compound registration error (CRE): mean spatial difference between stereotactic coordinates using (A) MRI-to-CT-to-CBCT and (B) MRI-to-CBCT. RESULTS The median (range) of TRE was 0.11 mm (0.06-0.22 mm), 0.17 mm (0.10-0.36 mm), and 0.12 mm (0.08-0.21 mm) for MRI-to-CT, MRI-to-CBCT, and CT-to-CBCT, respectively. The TRE for MRI-to-CBCT was statistically higher than the other 2 methods (P