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PURPOSE This study explored the value of flat detector C-arm CT-guidance system in performing percutaneous transthoracic needle biopsy (PTNB) for lung lesions in clinical practice. METHODS A total of 110 patients with solid lung lesions were enrolled to undergo PTNB procedures. The mean diameter of lesions was 4.63 cm (range, 0.6-15cm). The needle path was carefully planned and calculated on the C-arm CT system, which acquired three-dimensional CT-like cross-sectional images. The PTNB procedures were performed under needle guidance with fluoroscopic feedbacks. RESULTS Histopathologic tissue was successfully obtained from 108 patients with a puncture success rate of 98.2% (108/110). The diagnostic accuracy rate was found to be 96.3% (104/108). There was only one case of pneumothorax (0.9%) requiring therapy. The rates of mild pneumothorax and hemoptysis were low (12.0% and 6.5%, respectively). In addition, procedural time could be limited with this technique, which helped to reduce X-ray exposure. CONCLUSION Our study shows that C-arm CT-based needle guidance enables reliable and efficient needle positioning and progression by providing real-time intraoperative guidance. [ABSTRACT FROM AUTHOR]