RATIONALE AND OBJECTIVES: This study aimed to compare sub-solid nodule detection performances (SSNDP) on chest computed tomography (CT) with Adaptive Iterative Dose Reduction using Three Dimensional Processing (AIDR 3D) between 7 mAs (0.21 mSv) and 42 mAs (1.28 mSv) in total and in subgroups classified by nodular size, characteristics, and location, and analyze the association of SSNDP with size-specific dose estimate (SSDE). MATERIALS AND METHODS: As part of the Area-detector Computed Tomography for the Investigation of Thoracic Diseases Study, a Japanese multicenter research project, 68 subjects underwent chest CT with 120 kV, 0.35 seconds per rotation, and three tube currents: 240 mA (84 mAs), 120 mA (42 mAs), and 20 mA (7 mAs). The research committee of the study project outlined and approved our study protocols. The institutional review board of each institution approved this study. Axial 2-mm-thick CT images were reconstructed using AIDR 3D. Standard reference was determined by CT images at 84 mAs. Four radiologists recorded SSN presence by continuously distributed rating on CT at 7 mAs and 42 mAs. Receiver operating characteristic analysis was used to evaluate SSNDP at both doses in total and in subgroups classified by nodular longest diameter (LD) (≥5 mm), characteristics (pure and part-solid), and locations (ventral, intermediate, or dorsal; central or peripheral; and upper, middle, or lower). Detection sensitivity was compared among five groups of SSNs classified based on particular SSDE to nodule on CT with AIDR 3D at 7 mAs. RESULTS: Twenty-two part-solid and 86 pure SSNs were identified. For larger SSNs (LD ≥ 5 mm) as well as subgroups classified by nodular locations and part-solid nodules, SSNDP was similar in both methods (area under the receiver operating characteristics curve: 0.96 ± 0.02 in CT at 7 mAs and 0.97 ± 0.01 in CT at 42 mAs), with acceptable interobserver agreements in five locations. For larger SSNs (LD ≥ 5 mm), on CT at 42 mAs, no significant differences in detection sensitivity were found among the five groups classified by SSDE, whereas on CT with 7 mAs, four groups with SSDE of 0.65 or higher were superior in detection sensitivity to the other group, with SSDE less than 0.65 mGy. CONCLUSIONS: For SSNs with 5 mm or more in cases with normal range of body habitus, CT at 7 mAs was demonstrated to have comparable SSNDP to CT at 42 mAs regardless of nodular location and characteristics, and SSDE higher than 0.65 mGy is desirable to obtain sufficient SSNDP.