Background/Objectives: This study aimed to determine if MRI features can distinguish between spinal infections caused by pyogenic bacteria and Mycobacterium tuberculosis. Methods: Patients underwent an MRI of the thoracolumbar spine with and without contrast. Three blinded observers assessed the images, using statistical tests for analysis. Results: Demographic characteristics and symptom duration were similar between patients with tuberculous and pyogenic spinal infections. In 36 cases of pyogenic infections, the MRI showed weakly delineated paravertebral tissue enhancement (76%), a hyperintense signal in the T2 TIRM sequences (89%), and homogeneous vertebral body enhancement (89%). In 32 cases of Mycobacterium infections, the MRI revealed well-delineated paravertebral changes, mixed vertebral body signals, and variable enhancement. Pyogenic infections were more often found in the lumbar spine (67%) and typically involved two vertebrae, while tuberculous infections preferred the thoracic spine (75%) and often involved two vertebrae, with 25% affecting three or more vertebrae. Conclusions: The MRI features can help differentiate between pyogenic and tuberculous spine infections, though none are definitive. The study suggests that MRI can be used for initial differentiation or as a diagnostic tool when biopsy or surgical exploration is not possible.