Object Cone beam CT (CBCT) image guidance has recently been adopted for the delivery of spine radiosurgery. In 2007, the authors' institution began a dedicated spine radiosurgery program using the Elekta Synergy S system, which incorporates CBCT technology. In this study, the authors prospectively evaluated the Synergy S platform as a dedicated spine radiosurgery delivery system, including an evaluation of the accuracy of patient positioning using this technology, as part of a quality assurance program. Methods One hundred sixty-six spine and paraspinal lesions were treated using the Elekta Synergy S 6-MV LINAC with a beam modulator and CBCT image guidance combined with a HexaPOD couch that allows correction of patient positioning in 3 translational and 3 rotational directions. Stratifying the lesion by location, there were 28 cervical, 69 thoracic, 48 lumbar, and 21 sacral lesions. The most common histological types for the metastatic lesions (136 cases total) were breast, lung, sarcomas, and renal cells. The most common benign tumors (30 cases total) included 10 schwannomas, 5 neurofibromas, and 5 meningiomas. Twenty-eight lesions (17%) were intradural. To measure intratreatment patient movement, 3 quality assurance CBCTs were performed and recorded at separate times: immediately before treatment started; at the first third of the procedure; and at the second third of the procedure. The positioning data and fused images of the planning CT and CBCT were analyzed to determine intrafraction patient movements. From each of 3 quality assurance CBCT images, 3 translational and 3 rotational coordinates were obtained. Results The prescribed dose to the gross tumor volume, delivered in a single fraction, ranged from 12 to 20 Gy (mean 16 Gy) in this cohort. This dose was delivered by between 7 and 14 coplanar intensity-modulated radiation therapy beams (mean 9 beams). The gross tumor volumes ranged from 1.2 to 491.7 cm3 (mean 39.2 cm3). Mean treatment time including setup was 64 minutes. At the first third of the treatment, the magnitude of the 3D translational vector (X, Y, Z) was 1.1 ± 0.7 mm. Similarly, the 3D translational vector at the second third of the treatment was 1.0 ± 0.6 mm. The means ± SDs of the rotational angles were 0.2° ± 0.4°, 0.4° ± 0.5°, and 0.3° ± 0.5° along yaw, roll, and pitch, respectively, at the first third of the treatment, and 0.2° ± 0.3°, 0.4° ± 0.5°, and 0.4° ± 0.5°, respectively, at the second third of the treatment. Conclusions Single-fraction spine radiosurgery performed using the Synergy S platform and incorporating CBCT image guidance was determined to be feasible, accurate, and safe. This technique provides an overall translational position accuracy of < 2.0 mm.