The use of mapping to guide peripheral lung navigation (PLN) represents an advance in the management of peripheral pulmonary lesions (PPL). Software has been developed to virtually reconstruct computed tomography images into 3-dimensional airway maps and generate navigation pathways to target PPL. Despite this there remain significant gaps in understanding the factors associated with navigation success and failure including the cartographic performance characteristics of these software algorithms. This study was designed to determine whether differences exist when comparing PLN mapping platforms.An observational direct comparison was performed to evaluate navigation planning software packages for the lung. The primary endpoint was distance from the terminal end of the virtual navigation pathway to the target PPL. Secondary endpoints included distal virtual and segmental airway generations built to the target and/or in each lung.Twenty-five patient chest computed tomography scans with 41 PPL were evaluated. Virtual airway and navigation pathway maps were generated for each scan/nodule across all platforms. Virtual navigation pathway comparison revealed differences in the distance from the terminal end of the navigation pathway to the target PPL (robotic bronchoscopy 9.4 mm vs. tip-tracked electromagnetic navigation 14.2 mm vs. catheter based electromagnetic navigation 17.2 mm, P=0.0005) and in the generation of complete distal airway maps.Comparing PLN planning software revealed significant differences in the generation of virtual airway and navigation maps. These differences may play an unrecognized role in the accurate PLN and biopsy of PPL. Further prospective trials are needed to quantify the effect of the differences reported.