This study analyzes the homogeneity in liver attenuation of a body-weight-based protocol compared to a semi-fixed protocol. Patients undergoing abdominal multiphase computed tomography received 0.500 g of iodine (gI) per kilogram of body weight. Liver attenuation and enhancement were determined using regions of interest on scans in the pre-contrast and portal venous phases. The outcomes were analyzed for interpatient uniformity in weight groups. The subjective image quality was scored using a four-point Likert scale (excellent, good, moderate, and nondiagnostic). A total of 80 patients were included (56.3% male, 64 years, 78.0 kg) and were compared to 80 propensity-score-matched patients (62.5% male, 63 years, 81.7 kg). The liver attenuation values for different weight groups of the TBW-based protocol were not significantly different (p = 0.331): 109.1 ± 13.8 HU (≤70 kg), 104.6 ± 9.70 HU (70–90 kg), and 105.1 ± 11.6 HU (≥90 kg). For the semi-fixed protocol, there was a significant difference between the weight groups (p < 0.001): 121.1 ± 12.1 HU (≤70 kg), 108.9 ± 11.0 HU (70–90 kg), and 105.0 ± 9.8 HU (≥90 kg). For the TBW-based protocol, the enhancement was not significantly different between the weight groups (p = 0.064): 46.2 ± 15.1 HU (≤70 kg), 59.3 ± 6.8 HU (70–90 kg), and 52.1 ± 11.7 HU (≥90 kg). Additionally, for the semi-fixed protocol, the enhancement was not significantly different between the weight groups (p = 0.069): 59.4 ± 11.0 HU (≤70 kg), 53.0 ± 10.3 HU (70–90 kg), and 52.4 ± 7.5 HU (≥90 kg). The mean administered amount of iodine per kilogram was less for the TBW-based protocol compared to the semi-fixed protocol: 0.499 ± 0.012 and 0.528 ± 0.079, respectively (p = 0.002). Of the TBW-based protocol, 17.5% of the scans scored excellent enhancement quality, 76.3% good, and 6.3% moderate. Of the semi-fixed protocol, 70.0% scored excellent quality, 21.3% scored good, and 8.8% scored moderate. In conclusion, the TBW-based protocol increased the interpatient uniformity of liver attenuation but not the enhancement in the portal venous phase compared to the semi-fixed protocol, using an overall lower amount of contrast media and maintaining good subjective image quality.