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Background Context: Biopsy is important to obtain microbiological and histopathological diagnosis in spine infections and tumors. To date, there have been no prospective randomized trials comparing fluoroscopic guided and computed tomography (CT) transpedicular biopsy techniques. The goal of this study was to evaluate the accuracy, safety, and diagnostic outcome of these two diagnostic techniques., Purpose: To evaluate the accuracy, safety, and diagnostic outcome of fluoroscopic guided and CT transpedicular biopsy techniques., Study Design: Prospective randomized trial., Patient Sample: Sixty consecutive patients with clinical symptoms and radiological features suggestive of spinal infection or malignancy were recruited and randomized into fluoroscopic or CT guided spinal biopsy groups. Both groups were similar in terms of patient demographics, distribution of spinal infections and malignancy cases, and the level of biopsies., Outcome Measures: The primary outcome measure was diagnostic accuracy of both methods, determined based on true positive, true negative, false positive, and false negative biopsy findings. Secondary outcome measures included radiation exposure to patients and doctors, complications, and postbiopsy pain score., Methods: A transpedicular approach was performed with an 8G core biopsy needle. Specimens were sent for histopathological and microbiological examinations. Diagnosis was made based on biopsy results, clinical criteria and monitoring of disease progression during a 6-month follow up duration. Clinical criteria included presence of risk factors, level of inflammatory markers and magnetic resonance imaging findings. Radiation exposure to patients and doctors was measured with dosimeters., Results: There was no significant difference between the diagnostic accuracy of fluoroscopic and CT guided spinal biopsy (p=0.67) or between the diagnostic accuracy of spinal infection and spinal tumor in both groups (p=0.402 for fluoroscopy group and p=0.223 for CT group). Radiation exposure to patients was approximately 26 times higher in the CT group. Radiation exposure to doctors in the CT group was approximately 2 times higher compared to the fluoroscopic group if a lead shield was not used. Lead shields significantly reduced radiation exposure to doctors anywhere from 2 to 8 times. No complications were observed for either group and the differences in postbiopsy pain scores were not significant., Conclusions: The accuracy, procedure time, complication rate and pain score for both groups were similar. However, radiation exposure to patients and doctors were significantly higher in the CT group without lead protection. With lead protection, radiation to doctors reduced significantly., (Copyright © 2020 Elsevier Inc. All rights reserved.)