Purpose To measure the effect of reduced radiation exposure on low-contrast low-attenuation liver lesion detection in an anthropomorphic abdominal phantom by using filtered back projection (FBP) and sinogram-affirmed iterative reconstruction. Materials and Methods Eighteen radiologists blinded to phantom and study design interpreted randomized image data sets that contained 36 spherical simulated liver lesions of three sizes and three attenuation differences (5-mm diameter: 12, 18, and 24 HU less than the 90-HU background attenuation of the simulated liver insert; 10- and 15-mm diameter: 6, 12, and 18 HU less than the 90-HU background attenuation) scanned with four discrete exposure settings and reconstructed by using FBP and sinogram-affirmed iterative reconstruction. Response assessment included region-level lesion presence or absence on a five-point diagnostic confidence scale. Statistical evaluation included multireader multicase receiver operating characteristic curve analysis, with nonparametric methods and noninferiority analysis at a margin of -0.10. Results Pooled accuracy at 75% exposure for both FBP and sinogram-affirmed iterative reconstruction was noninferior to 100% exposure (P = .002 and P < .001, respectively). Subsequent exposure reductions resulted in a significant decrease in accuracy. When the smallest (5-mm-diameter) lesions were excluded from analysis, sinogram-affirmed iterative reconstruction was superior to FBP at 100% exposure (P = .011), and sinogram-affirmed iterative reconstruction at 25% and 50% exposure reduction was noninferior to FBP at 100% exposure (P ≤ .013). Reader confidence was greater with sinogram-affirmed iterative reconstruction than with FBP for 10- and 15-mm lesions (2.94 vs 2.76 and 3.62 vs 3.52, respectively). Conclusion In this low-contrast low-attenuation liver lesion model, a 25% exposure reduction maintained noninferior diagnostic accuracy. However, detection was inferior with each subsequent exposure reduction, regardless of reconstruction method. Sinogram-affirmed iterative reconstruction and FBP performed equally well at modest exposure reduction (25%-50%). Readers had higher confidence levels with sinogram-affirmed iterative reconstruction for the 10- and 15-mm lesions.