OBJECTIVE: The purpose of this article is to assess detection, tracking, and reading time of solid lung nodules > or = 4 mm on pairs of MDCT chest screening examinations using a computer-aided detection (CAD) system. MATERIALS AND METHODS: Of 54 pairs of low-dose MDCT chest examinations (1.25-mm collimation), two chest radiologists in consensus established that 25 examinations contained 52 nodules > or = 4 mm. All paired examinations were interpreted on the CAD workstation--first without and then with CAD input--for the detection and tracking of lung nodules. A subset of 33 examination pairs was later read on the clinical workstation used in daily practice, and the results were compared for reading time with those on the CAD workstation. RESULTS: After CAD input, the sensitivity for nodule detection increased statistically significantly for both readers (9.6% and 23%; p < or = 0.025). One cancer initially missed by one radiologist was correctly identified with CAD input. The overall reading time on the CAD workstation and clinical workstation was comparable for both radiologists. On average, readers spent 4-5 minutes per case to read the paired examinations on the CAD workstation and 6-8 seconds per CAD mark. The CAD system successfully matched 91.3% of nodules detected in both examinations. The overall rate of available CAD growth assessment was 54.9% of all nodule pairs. CONCLUSION: In the context of temporal comparison of MDCT screening examinations, the sensitivity of radiologists for detecting lung nodules > or = 4 mm increased significantly (p < or = 0.025) with CAD input without compromising reading time.