Purpose: To evaluate a new miniature optical navigation system for CT-guided liver interventions. Material and Methods: A two-center, prospective study was performed with four interventional radiologists. A total of 20 patients had CT-guided liver biopsy or ablation interventions utilizing the CT-Guide^? navigation system (ActiViews Inc., Wakefield, MA) between July 2011 and December 2011. The navigation system consists of a self-adhesive patientsticker printed with coincident colored and radio-opaque reference markers, a miniature disposable video camera that clips on and off an interventional instrument, and software loaded on a computer to display the navigation information. The primary end point was the frequency of a satisfactory instrument position for the intended intervention. Results: The cohort consisted of 13 males and 7 females with an average age of 63.1 years (range of 38 to 80). Most of the patients, 70%, underwent CT-guided liver biopsy while the remainder had CT-guided ablation therapy. The average lesion size was 3.1 cm (range of 1.1 - 6.9 cm). All of the interventions, regardless of lesion size, met the primary end point of satisfactory instrument positioning. There were no device-related or unexpected adverse events recorded. Only one patient had a mild adverse event and it resolved without intervention. Conclusions: This study demonstrated the safety and effectiveness of the CT-Guide^? navigation system for CT-guided liver interventions, for both biopsies and ablations. The targeting success rate for a satisfactory intervention was 100% with the system.