The purpose of this study was to compare a routine bone SPECT/CT protocol using CT reconstructed with filtered backprojection (FBP) with an optimized protocol using low-dose CT images reconstructed with adaptive statistical iterative reconstruction (ASiR). In this prospective study, enrolled patients underwent bone SPECT/CT, with 1 SPECT acquisition followed by 2 randomized CT acquisitions: FBP CT (FBP; noise index, 25) and ASiR CT (70% ASiR; noise index, 40). The image quality of both attenuation-corrected SPECT and CT images was visually (5-point Likert scale, 2 interpreters) and quantitatively (contrast ratio [CR] and signal-to-noise ratio [SNR]) estimated. The CT dose index volume, dose-length product, and effective dose were compared. Seventy-five patients were enrolled in the study. Quantitative attenuation-corrected SPECT evaluation showed no inferiority for contrast ratio and SNR issued from FBP CT or ASiR CT (respectively, 13.41 ± 7.83 vs. 13.45 ± 7.99 and 2.33 ± 0.83 vs. 2.32 ± 0.84). Qualitative image analysis showed no difference between attenuation-corrected SPECT images issued from FBP CT or ASiR CT for both interpreters (respectively, 3.5 ± 0.6 vs. 3.5 ± 0.6 and 3.6 ± 0.5 vs. 3.6 ± 0.5). Quantitative CT evaluation showed no inferiority for SNR between FBP and ASiR CT images (respectively, 0.93 ± 0.16 and 1.07 ± 0.17). Qualitative image analysis showed no quality difference between FBP and ASiR CT images for both interpreters (respectively, 3.8 ± 0.5 vs. 3.6 ± 0.5 and 4.0 ± 0.1 vs. 4.0 ± 0.2). Mean CT dose index volume, dose-length product, and effective dose for ASiR CT (3.0 ± 2.0 mGy, 148 ± 85 mGy⋅cm, and 2.2 ± 1.3 mSv) were significantly lower than for FBP CT (8.5 ± 3.7 mGy, 365 ± 160 mGy⋅cm, and 5.5 ± 2.4 mSv). The use of 70% ASiR blending in bone SPECT/CT can reduce the CT radiation dose by 60%, with no sacrifice in attenuation-corrected SPECT and CT image quality, compared with the conventional protocol using FBP CT reconstruction technique.