Purpose To evaluate the use of susceptibility-weighted MRI for the differentiation of predominantly osteoblastic and osteolytic spine metastases. Materials and Methods For this prospective study, 53 study participants (mean age, 54.5 years ± 14.3 [range, 22-88 years]; 27 men with a mean age of 55.3 years ± 12.7 [range, 22-72 years] and 26 women with a mean age of 53.8 years ± 15.7 [range, 23-88 years]) with clinically suspected spine metastases underwent imaging with standard MRI sequences, susceptibility-weighted MRI, and CT. Sensitivities and specificities of MRI sequences for the detection of predominantly osteoblastic and osteolytic metastases were determined by using CT as the reference standard. The metastases-to-vertebral body signal intensity ratio (MVR) was calculated to compare modalities. Phantom measurements were obtained to correlate bone densities between MRI sequences and CT. Results A total of 64 metastases (38 predominantly osteoblastic, 26 predominantly osteolytic) were detected. Susceptibility-weighted MRI achieved a sensitivity of 100% (38 of 38) and specificity of 96% (25 of 26) for predominantly osteoblastic metastases and a sensitivity of 96% (25 of 26) and specificity of 100% (38 of 38) for predominantly osteolytic metastases. Standard MRI sequences achieved a sensitivity of 89% (34 of 38) and specificity of 73% (19 of 26) for predominantly osteoblastic metastases and a sensitivity of 73% (19 of 26) and specificity of 92% (35 of 38) for predominantly osteolytic metastases. MVR measurements obtained with susceptibility-weighted MRI demonstrated a strong correlation with those obtained with CT (R2 = 0.75), whereas those obtained with T1-weighted MRI, T2-weighted MRI, and turbo inversion-recovery magnitude MRI showed a weak to moderate correlation (R2 = 0.00, R2 = 0.35, and R2 = 0.39, respectively). Susceptibility-weighted MRI showed a strong correlation with CT with regard to metastases size (R2 = 0.91). In phantom measurements, susceptibility-weighted MRI enabled the reliable differentiation of different degrees of mineralization (R2 = 0.92 compared with CT). Conclusion Susceptibility-weighted MRI enables the reliable differentiation between predominantly osteoblastic and osteolytic spine metastases with a higher accuracy than standard MRI sequences. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Schweitzer in this issue.