Background: Pain following spinal cord injury (SCI) has proved difficult to treat. Although the use of antiepileptic drugs to treat SCI-related pain has been studied previously, topiramate has not been investigated in this population. Our recent experience suggests that topiramate may be efficacious in the treatment of SCI-related pain. Method: Case Studies Findings: This report presents the clinical histories of two people with pain following SCI who reported beneficial effects of treatment with the new antiepileptic drug topiramate, even after failing treatment with standard analgesic medications. Topiramate was well tolerated in these patients. Conclusion: For post-SCI pain, topiramate appears to be an effective treatment in some patients. Based on the present anecdotal findings, larger controlled studies comparing topiramate with standard treatment for SCI-related pain are warranted.