BACKGROUND: Therapy using a targeted epidural blood patch (EBP) has been linked to cerebrospinal fluid (CSF) hypovolemia syndrome empirically, when conservative therapies failed to relieve headaches. The aim of this study is to investigate the effectiveness of EBP, for those who are refractory to conservative therapy, as a treatment for syndrome of CSF hypovolemia. METHODS: Sixteen patients were studied, where six patients were treated with conservative therapy and 10 patients were treated with EBP. After the treatments, we evaluated the difference in the duration of headaches between the two groups. With the patients treated with EBP, we also evaluated the differences in the duration of headaches between those with or without pachymeningeal enhancement on a brain MRI, and those with or without CSF leakage site on RI cisternography. RESULTS: Mean duration (1.30 +/- 0.48 days) of headaches in those treated with EBP was significantly shorter than in those without EBP (p=0.022). There was no significant difference in duration of headaches between those with and without pachymeningeal enhancement in a brain MRI. There was also no significant difference in duration of headache between those with and without CSF leakage in RI cisternography. CONCLUSIONS: The EBP is an effective therapy for syndrome of CSF hypovolemia regardless of pachymeningeal enhancement in a brain MRI and CSF leakage in RI cisternography when conservative therapies fail to relieve headaches.