To benchmark the performance of state-of-the-art computer-aided detection (CAD) of pulmonary nodules using the largest publicly available annotated CT database (LIDC/IDRI), and to show that CAD finds lesions not identified by the LIDC's four-fold double reading process.The LIDC/IDRI database contains 888 thoracic CT scans with a section thickness of 2.5A,A mm or lower. We report performance of two commercial and one academic CAD system. The influence of presence of contrast, section thickness, and reconstruction kernel on CAD performance was assessed. Four radiologists independently analyzed the false positive CAD marks of the best CAD system.The updated commercial CAD system showed the best performance with a sensitivity of 82A,A % at an average of 3.1 false positive detections per scan. Forty-five false positive CAD marks were scored as nodules by all four radiologists in our study.On the largest publicly available reference database for lung nodule detection in chest CT, the updated commercial CAD system locates the vast majority of pulmonary nodules at a low false positive rate. Potential for CAD is substantiated by the fact that it identifies pulmonary nodules that were not marked during the extensive four-fold LIDC annotation process.