Objectives The aim of this study is to introduce the infrapedicular approach to CT-guided spine interventions, a specialized technique that can safely expand the scope of spine lesions amenable to treatment, and to document the feasibility in a variety of procedural scenarios to the extent possible with a retrospective case series. Methods Data from 24 cases performed at a single institution over a 10-year period were retrospectively reviewed to assess the technical feasibility and safety profile of the technique. Results The infrapedicular approach enabled a technically satisfactory procedural result in 24 cases (mean age 63.9 years, range 35–83 years). Two peri-procedural complications occurred, including a small pneumothorax and a cerebrospinal fluid leak, both of which resolved with conservative treatment. No lasting injurious effects or additional complications were identified. The infrapedicular approach was found to be particularly useful in multiple technically challenging scenarios: it facilitates access to lesions in the inferior vertebral body, allows biopsy, cement augmentation, or ablation of high thoracic lesions difficult to treat due to limitations of steep angulation of fluoroscopy and CT scanners, and enables treatment of large lesions by using multiple overlapping probes.