BACKGROUND Bronchoscopic lung biopsy using fluoroscopic guidance is the standard procedure for the diagnosis of peripheral pulmonary lesions. Peripheral lesions can also be biopsied using endobronchial ultrasound (EBUS) guidance, which is equally effective and does not expose the patient or staff to radiation. OBJECTIVE We determined the diagnostic yield of EBUS- and fluoroscopic-guided bronchoscopic lung biopsy (BLB) under everyday, clinical conditions, and compared our results to published data. METHODS A total of 304 consecutive patients with peripheral pulmonary lesions who underwent EBUS- or fluoroscopy-guided BLB were included in this study. We compared the diagnostic yield of EBUS- and fluoroscopy-guided bronchoscopic lung biopsy (BLB) to determine which method is more sensitive for the diagnosis of peripheral pulmonary lesions. RESULTS EBUS-guided BLB was performed in 116 patients, and fluoroscopy-guided BLB was used in 188. The median diameter of the peripheral pulmonary lesions in the EBUS group was 31.5 mm (9-125) compared with 34.5 mm (6-100) in the fluoroscopy group. Diagnostic biopsy samples were obtained from 89 (77%) patients using EBUS and from 139 (74%) patients using fluoroscopy-guided BLB. The difference in the diagnostic outcome between these methods was not statistically significant. CONCLUSIONS The results of our study showed that the diagnostic yield was similar between EBUS- and fluoroscopy-guided BLB, although our findings suggest that more positive outcomes are expected with EBUS. The EBUS procedure is safer because it does not involve exposure of the patient or medical staff to radiation.