Multiple myeloma (MM) is a clonal plasma cell disorder originating in bone marrow. Whole body low-dose multidetector CT (MDCT) can depict bone marrow infiltration by myeloma cells into the adipose-rich fatty marrow of the appendicular skeleton. However, automated and objective volume measurement of bone marrow infiltration has not been established, and its clinical relevance remains unclear. We therefore developed novel CT post-processing software (MABLE software) and measured the total sum of CT values (cumulative CT value, cCTv) representing bone marrow infiltration, by combining volume and voxel-based CT values. The cCTv was greater in patients with symptomatic MM than in those with smouldering MM or monoclonal gammopathy of unknown significance. Patients with revised International Staging System (R-ISS) III had a higher cCTv than those with R-ISS I or II. Age, albumin, and M-protein levels independently predicted cCTv. Mixed graphical model analysis revealed direct relationships between cCTv and age or R-ISS. Tree-structured survival analysis and multivariate Cox analysis revealed that a cCTv greater than or equal to 4.4 was independently prognostic for overall survival. Anti-myeloma therapy reduced cCTv after treatment. These findings suggest that the automatically calculated cCTv reflects disease aggressiveness and is useful for accurate prognostic prediction in MM patients.