Post-dural puncture headache (PDPH) is a vexing problem of the patients following spinal anesthesia or a complication relative to inadvertent dural puncture in epidural anesthesia. The prevention and management of PDPH contain a laddered forestallment and therapy with varying results. The anticonvulsant gabapentin has been reported to be effective in prophylaxis and treatment of headaches. We report here two cases of PDPH, who failed to respond to traditional analgesics, but had good response to gabapentin. After treatment with gabapentin 400 mg three times daily, the headache was relieved remarkably in 24 hr. Discussions of the pathophysiology of PDPH, pharmacological actions of gabapentin, and possible mechanisms of action of gabapentin on PDPH are brought forward in the text.