Purpose To evaluate the effect of iterative reconstruction on the depiction of systemic sclerosis–related interstitial lung disease (ILD) when the radiation dose is reduced by 60%. Materials and Methods This study was based on retrospective interpretation of prospectively acquired data over a 12-month period and approved by the institutional review board. The requirement to obtain informed consent was waived. Fifty-five chest computed tomographic (CT) examinations were performed in 38 women and 17 men (mean age, 55.8 years; range, 23–82 years) by using a dual-source CT unit with (a) both tubes set at similar energy (120 kVp) and (b) the total reference milliampere seconds (ie, 110 mAs) split up in a way that 40% was applied to tube A and 60% to tube B. Two series of images were generated simultaneously from the same dataset: (a) standard-dose images (generated from both tubes) reconstructed with filtered back projection (group 1, the reference standard) and (b) reduced-dose images (generated from tube A; 60% dose reduction) reconstructed with sinogram-affirmed iterative reconstruction (SAFIRE) (group 2). In both groups, the analyzed parameters comprised the image noise and the visualization and conspicuity of CT features of ILD. Two readers independently analyzed images from both groups. Results were compared by using the Wilcoxon test for paired samples; the 95% confidence interval was calculated when appropriate. Results The mean level of objective noise in group 2 was significantly lower than that in group 1 (22.02 HU vs 26.23 HU, respectively; P < .0001). The CT features of ILD in group 1 were always depicted in group 2, with subjective conspicuity scores (a) improved in group 2 for ground-glass opacity, reticulation, and bronchiectasis and/or bronchiolectasis and (b) identical in both groups for honeycombing. The interobserver agreement for their depiction was excellent in both groups (κ, 0.84–0.98). Conclusion Despite a 60% dose reduction, images reconstructed with SAFIRE allowed similar detection of systematic sclerosis–related ILD compared with the reference standard.