To test the feasibility of ultra-low-dose (ULD) computed tomography (CT) combined with an artificial intelligence iterative reconstruction (AIIR) algorithm for screening pulmonary nodules using computer-assisted diagnosis (CAD).A chest phantom with artificial pulmonary nodules was first scanned using the routine protocol and the ULD protocol (3.28 versus 0.18 mSv) to compare the image quality and to test the acceptability of the ULD CT protocol. Next, 147 lung-screening patients were enrolled prospectively, undergoing an additional ULD CT immediately after their routine CT examination for clinical validation. Images were reconstructed with filtered back-projection (FBP), hybrid iterative reconstruction (HIR), the AIIR, and were imported to the CAD software for preliminary nodule detection. Subjective image quality on the phantom was scored using a five-point scale and compared using the Mann-Whitney U-test. Nodule detection using CAD was evaluated for ULD HIR and AIIR images using the routine dose image as reference.Higher image quality was scored for AIIR than for FBP and HIR at ULD (p<0.001). As reported by CAD, 107 patients were presented with more than five nodules on routine dose images and were chosen to represent the challenging cases at an early stage of pulmonary disease. Among such, the performance of nodule detection by CAD on ULD HIR and AIIR images was 75.2% and 92.2% of the routine dose image, respectively.Combined with AIIR, it was feasible to use an ULD CT protocol with 95% dose reduction for CAD-based screening of pulmonary nodules.Copyright © 2023. Published by Elsevier Ltd.