The aims of this study were to assess the visibility of pulmonary structures in patients with cystic fibrosis (CF) in digital tomosynthesis (DTS) using computed tomography (CT) as reference and to investigate the dependency on anatomical location and observer experience. Anatomical structures in predefined regions of CT images from 21 patients were identified. Three observers with different levels of experience rated the visibility of the structures in DTS by performing a head-to-head comparison with visibility in CT. Visibility of the structures in DTS was reported as equal to CT in 34 %, inferior in 52 % and superior in 14 % of the ratings. Central and peripheral lateral structures received higher visibility ratings compared with peripheral structures anteriorly, posteriorly and surrounding the diaphragm (p ≤ 0.001). Reported visibility was significantly higher for the most experienced observer (p ≤ 0.01). The results indicate that minor pathology can be difficult to visualise with DTS depending on location and observer experience. Central and peripheral lateral structures are generally well depicted.