BackgroundAlthough the basic pathophysiology is the same in both cervical and thoracolumbar intervertebral disk (IVD) extrusions, there are considerable clinical differences that have only been partially explained.Hypothesis/ObjectivesThe epidural inflammatory response differs between cervical and thoracolumbar IVD extrusions.AnimalsFifty‐five dogs with cervical and 80 dogs with thoracolumbar IVD extrusions.MethodsClinical data and histopathologic variables were investigated. Associations between severity of epidural inflammation and clinical and pathologic variables, impact of chondrodystrophic phenotype, and localization (cervical versus thoracolumbar) were evaluated statistically.ResultsDogs with cervical IVD extrusion were significantly older (P < 0.001), had less severe and longer duration of neurologic signs (both P < 0.001), were more painful (P = 0.038), and had a better outcome (P = 0.005) than dogs with a thoracolumbar IVD extrusion. On histopathology, cervical epidural material had less severe calcification (P = 0.002) and inflammation (P < 0.001). No significant differences regarding chondrodystrophic phenotype were found.Conclusion and Clinical ImportanceThere was significantly less intensive inflammatory response in the cervical epidural space. This observation correlated positively with less nucleus pulposus calcification in cervical extrusions indicating biochemical, metabolic, and biomechanical differences between the 2 locations, which remain to be characterized in future studies.