The aim of this study is to evaluate the feasibility, safety, and clinical efficacy of CT-guided 125I seed interstitial brachytherapy in patients with recurrent spinal metastases after external beam radiotherapy (EBRT). Between August 2003 and September 2015, 26 spinal metastatic lesions (24 patients) were reirradiated by this salvage therapy modality. Treatment for all patients was preplanned using a three-dimensional treatment planning system 3-5 days before 125I seed interstitial brachytherapy; dosimetry verification was performed immediately after seed implantation. Median actual D90 was 99 Gy (range, 90-176), and spinal cord median Dmax was 39 Gy (range, 6-110). Median local control (LC) was 12 months (95% CI: 7.0-17.0). The 6- and 12-month LC rates were 52% and 40%, respectively. Median overall survival (OS) was 11 months (95% CI: 7.7-14.3); 6-month and 1-, 2-, and 3-year OS rates were 65%, 37%, 14%, and 9%, respectively. Pain-free survival ranged from 2 to 42 months (median, 6; 95% CI: 4.6-7.4). Treatment was well-tolerated, with no radiation-induced vertebral compression fractures or myelopathy reported. Reirradiation with CT-guided 125I seed interstitial brachytherapy appears to be feasible, safe, and effective as pain relief or salvage treatment for patients with recurrent spinal metastases after EBRT.