Purpose: To evaluate the reproducibility of liver tumor attenuation measurement performed by using the routinely used manual region-of-interest (ROI) method and that of measurement performed by using a semiautomated volumetric approach at computed tomography (CT). Materials and Methods: This HIPAA-compliant retrospective study had institutional review board approval. The requirement for patient informed consent was waived. Attenuation of colon cancer liver metastases in 208 patients was measured on portal venous phase multidetector CT images by using a single ROI, the average measurement in three ROIs on a single section, and with semiautomated segmentation of the entire tumor volume (volumetric attenuation) to evaluate intermethod agreement. Intraobserver and interobserver reproducibility were evaluated in the first 70 patients. Measurements were repeated after 30 days to assess intraobserver reproducibility. Differences between methods were tested by using repeated-measures analysis of variance. Intermethod, intraobserver, and interobserver agreements were tested by using Bland-Altman analysis and the Lin concordance correlation coefficient (ρ c). P < .05 was considered to indicate a significant difference. Results: A total of 208 pathologically proven colon cancer hepatic metastases larger than 20 mm in diameter in 100 women and 108 men (mean age, 61.6 years ± 11.6 [standard deviation]; range, 28-87 years) were evaluated. Attenuation was significantly different between the three methods of measurement (P < .001 for all). Volumetric measurements had better intraobserver agreement (precision = 3.3%, ρ c= 0.996, P < .001) than single-ROI measurements (precision = 12.0%, ρ c = 0.947, P < .001) and measurements averaged over three ROIs (precision = 9.3%, ρ c = 0.965, P < .001). Volumetric measurements also had better interobserver agreement (precision = 3.6%, ρ c = 0.993, P < .001) than single-ROI measurements (precision = 11.3%, ρ c = 0.957, P < .001) and the average measurement in three ROIs (precision = 8.5%, ρ c = 0.976, P < .001). Conclusion: Measurements of hepatic tumor attenuation at multidetector CT are reproducible. An approach based on the evaluation of whole-lesion attenuation demonstrated better reproducibility than ROI measurements.