In patients with spinal instability, spinal cord compression, or neurologic deficits from spine metastases, the standard of care is surgical decompression/stabilization followed by radiation therapy (RT). Recurrence rates following conventional RT to the post-operative spine remain high. Retrospective data suggests improved local control following spine SBRT in the post-operative setting, however prospective data are limited. The purpose of this study is to prospectively examine the efficacy of post-operative SBRT in patients who have undergone surgical resection of metastatic spine disease. We hypothesize that post-operative SBRT to the spine would be associated with higher local control than historical rates following conventional RT. A total of 35 adult patients with a KPS ≥40 and spine metastases from solid tumors s/p any extent of resection with no prior overlapping RT and target volumes ≤3 consecutive vertebral levels were enrolled. GTV was defined as residual disease on post-operative MRI. The CTV was the GTV, tumor bed, all sites of disease based on pre-operative imaging/operative findings plus the adjacent anatomic compartment. The PTV was a 1-2 mm radial expansion. The spinal cord was defined on T2 weighted MRI or CT myelogram in patients with surgical instrumentation. The cord planning risk volume was the cord plus a 2 mm radial expansion or the thecal sac. All patients received SBRT 30 Gy in 5 fractions. Patients were followed with neurologic exam and CT and/or MRI every 3 months. Neurologic function was assessed at the same time points using the ASIA impairment score. Pain was rated according to the 10-point visual analog scale and MDACC brief pain index. Toxicity was recorded according to NCI CTCAE v4. The primary objective was the rate of radiographic local recurrence at 12 months following completion of SBRT. Patient characteristics: 26% had radio-resistant primaries; 76% were ASIA E and the remainder ASIA D; the median baseline KPS was 70 (range 50-100). The median prescription isodose line was 61% (range: 53-71) with a median coverage of the PTV of 90.2% (range 85.1-96.2). 31 patients have reached 12 months follow-up. Radiographic and symptomatic local control at 1 year were 90% (95% confidence interval: 74%-98%). The median time to recurrence in these 3 patients was 3.5 months (range 3.4-5.8 months), all had radio-sensitive tumors, and all recurrences included an epidural component. 22.5% of patients developed recurrence or progression within 1 vertebral body of the target. No patients experienced wound dehiscence, hardware failure or radiation induced spinal cord myelopathy. The median time to return to systemic therapy was 0.5 months (range 0-9.4 months). This prospective study of post-operative spine SBRT demonstrates excellent local control with low toxicity. These data suggest superior rates of local control compared to conventional RT, however a formal comparative study is warranted.