<b><i>Background:</i></b> Digital fluoroscopic tomosynthesis-guided electromagnetic navigational bronchoscopy (F-ENB) is a novel adjunct to ENB associated with higher diagnostic yield. The likelihood of F-ENB allowing accurate placement of a biopsy needle within a target remains unclear. <b><i>Objective:</i></b> This study intends to determine the accuracy of F-ENB as confirmed by cone-beam computed tomography (CBCT) scan. <b><i>Methods:</i></b> Patients undergoing CBCT-assisted ENB for lung nodule biopsy were prospectively enrolled. ENB was performed followed by digital tomosynthesis correction. Once optimal F-ENB alignment was achieved, and a needle was advanced into the expected location of the nodule followed by CBCT. The primary outcome was the percentage of “needle-in-lesion” hits, defined as needle tip within the nodule in 3 planes. Secondary outcomes were diagnostic yield, procedure and room time, complications, radiation, and distance between the needle tip and nodule. <b><i>Results:</i></b> Twenty-six patients with a total of 29 nodules were enrolled. Mean nodule size was 13 mm (±4 mm) in maximal axial dimension, 83% (<i>n</i> = 24) were located in the peripheral third of the chest, and 17% (<i>n</i> = 5) had a bronchus sign. F-ENB guidance resulted in needle-in-lesion in 21 of 29 nodules (72%). Mean needle tip-to-nodule distance for nonhits was 1.75 mm (±1.35 mm). There were no complications. <b><i>Conclusion:</i></b> F-ENB resulted in a needle-in-lesion biopsy in greater than 70% of nodules despite features traditionally associated with poor diagnostic yield (size, absence of bronchus sign). Mean distance between needle tip and target for nonhits was less than 2 mm. These data suggest F-ENB alignment is accurate for small peripheral nodules.