<b><i>Background:</i></b> The diagnostic yield of peripheral pulmonary lesions (PPLs) using radial endobronchial ultrasound (EBUS) remains challenging without navigation systems. Cone-beam computed tomography-derived augmented fluoroscopy (CBCT-AF) represents a recently developed technique, and its clinical utility remains to be investigated. <b><i>Objectives:</i></b> The aim of this study was to investigate the diagnostic yield of transbronchial biopsy (TBB) using a combination of CBCT-AF and radial EBUS. <b><i>Methods:</i></b> We recruited consecutive patients with PPLs who underwent radial EBUS-guided TBB, with or without AF, between October 2018 and July 2019. Following propensity score 1:1 matching, we recorded the procedure-related data and measured their efficacy and safety. <b><i>Results:</i></b> While 72 patients received EBUS-plus-AF, 235 patients received EBUS only. We included 53 paired patients following propensity score matching. The median size of lesions was 2.8 and 2.9 cm in the EBUS-plus-AF group and EBUS-only group, respectively. Diagnostic yield was higher in the former group (75.5 vs. 52.8%; <i>p</i> = 0.015). The diagnostic yield for the EBUS-plus-AF group was significantly higher for lesions ≤30 mm (73.5 vs. 36.1%; <i>p</i> = 0.002). Moreover, there was no significant difference in the complication rates (3.8 vs. 5.7%; <i>p</i> = 1.000). Twenty-four nodules (45.3%) were invisible by fluoroscopy in the EBUS-plus-AF group. All of them were identifiable on CBCT images and successfully annotated for AF. The mean radiation dose of total procedure, CBCT, and fluoroscopy was 19.59, 16.4, and 3.17 Gy cm<sup>2</sup>, respectively. <b><i>Conclusions:</i></b> TBB using a combination of CBCT-AF and EBUS resulted in a satisfactory diagnostic yield and safety.