Objectives To illuminate the prognostic value of ADC (apparent diffusion coefficient), an important quantitative parameter of diffusion-weighted MRI, for multiple myeloma (MM). Methods A prospective single-center study which enrolled 114 consecutive newly diagnosed MM patients with baseline whole-body diffusion-weighted MRI (WB DW-MRI) results was conducted. Baseline clinical and MRI parameters were analyzed with univariate and multivariate approaches to identify independent risk factors for progression-free survival (PFS) and overall survival (OS). Results Five different DW-MRI patterns were seen, and the mean ADC value of the representative background bone marrow was 0.4662 +/- 0.1939 x 10(-3)mm(2)/s. After a mean follow-up of 50.2 months (range, 15.7-75.8 months), twenty-four patients died and seven were lost to follow-up. The mean ADC value of the representative background bone marrow was showed to be an independent risk factor for both PFS (HR 4.664; 95% confidence interval (CI) 1.138-19.121;p= 0.032) and OS (HR 14.130; 95% CI 1.544-129.299;p= 0.019). Normal/salt-and-pepper pattern on DW-MRI was associated with PFS using univariate analysis (p= 0.035) but lost the significance with multivariate Cox regression. Conclusions Mean ADC value of the representative background bone marrow predicts both PFS and OS which suggests the role of baseline DW-MRI for risk stratification in newly diagnosed MM patients.