Objective: The purpose of our study was to evaluate the diagnostic accuracy of transthoracic fine-needle aspiration biopsy (TFNAB) using a C-arm cone-beam CT (CBCT) system and to assess risk factors for immediate post-procedural complications in patients with lung lesions. Methods: From October 2007 to April 2009, 94 TFNAB procedures using a C-arm system were studied in 91 patients with pulmonary lesions a chest CT scans. We retrospectively reviewed the patients' radiological and histopathological findings. We evaluated the lesion size, lesion abutted to pleura and presence or absence of emphysema along the needle path, lesion depth, visibility of target lesion and patient's position. Pneumothorax and pulmonary haemorrhage were assessed after TFNAB. Overall diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were analysed. Results: In 94 TFNAB procedures, 58 lesions were malignant and 36 were benign. The sensitivity, specificity, PPV, NPV and overall diagnostic accuracy rate of TFNAB were 93.1%, 100%, 100%, 90% and 97.9%, respectively. Pneumothorax was developed in 24 procedures. None of the parameters showed significant impact on the frequency of the pneumothorax. Overall haemorrhage occurred in 43 procedures. The incidence of overall haemorrhage was higher in patients with smaller lesions, longer pleural distance and pleural abutted lesions (p,0.05). Differences in visibility at projection radiographs were statistically significant between patients with or without perilesional haemorrhage (p,0.05). Conclusion: Transthoracic fine-needle aspiration biopsy using a C-arm CBCT system is feasible for imaging guidance of lung lesion and early detection of the proceduralrelated complications.