Objective Previously we proposed using an interpolated average computed tomography (IACT) method as a lowdose alternate of cine average computed tomography (CACT) for PET attenuation correction (AC). This study aims to evaluate its performance for thoracic lesions with different characteristics in simulations and clinical patients. Materials and methods We used the XCAT phantom to simulate noisy fluorine-18 fluorodeoxyglucose (18F-FDG) distribution with respiratory motion amplitudes of 2 and 3 cm. Average activity and attenuation maps represented static PET and CACT, respectively. IACT was generated by the end-inspiration and end-expiration phases of the attenuation maps (HCT-in and HCT-ex) using a deformable registration method. Spherical lesions with diameters of 10 and 20 mm with four target-to-background ratios (TBRs) were simulated at four different locations individually, including the lower left lung, lower right lung, middle right lung, and upper right lung. Five patients with a total of six thoracic lesions were recruited. They were scanned 1 h after 315–480 MBq 18F-FDG injection. Simulated and clinical PET sinograms were reconstructed with AC using (i) CACT, (ii) IACT, and (iii) helical computed tomography (HCTs). The TBRs and mean standardized uptake value were analyzed. Results Significant artifacts were observed in PETHCTs from visual assessment. For both simulation and clinical study, PETIACT was more similar to PETCACT in terms of TBRs and mean standardized uptake value. The differences between CACT/IACT and HCTs were more significant for lesions located at the lower lungs. Conclusion The IACT is a robust and low-dose AC method for improved thoracic lesion localization and quantitation for a wide range of lesion characteristics. Nucl Med Commun 37:297–306 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.