Epidural steroid injections are commonly used in the treatment of low back pain and radiculopathy based on their antiinflammatory and analgesic benefits. However, steroids are known to affect collagen synthesis, material strength, and tissue healing. The purpose of this study was to assess the effects of serial epidural steroid injections on the material properties of the lumbar dura mater. Serial epidural steroid injections of saline or methylprednisolone at 2-week intervals were performed in three paired groups of canines; a separate noninjected group was used as controls. Postmortem, dural sample testing to failure and histologic analysis was performed. Mechanical failure testing revealed no clinically significant change in the transverse dorsal dura tensile strength between all saline-injected, steroid-injected, or noninjected controls. Histologic analysis demonstrated no overt disruption of collagen matrix organization; however, electron microscopy demonstrated a significant decrease in the number of intracytoplasmic mitochondria of dural fibroblasts in steroid-injected animals, suggesting a metabolic inhibitory effect within steroid-injected dura mater. In the clinical time frame of this study, serial epidural steroid injections appeared to produce no significant material or matrix changes in the lumbar dura.