The aim of this study was to evaluate the efficacies and compare the outcomes of targeted and blind epidural blood patch (EBP) treatments of spontaneous intracranial hypotension (SIH). Between January 1999 and December 2009, 56 patients who were diagnosed with SIH received either a targeted or blind EBP. The efficacies of targeted and blind EBPs were evaluated based on degree and duration of symptom relief and on the need for repeat EBP. Fifty-six patients (23 men and 33 women; mean age, 39.6 years; age range, 22-69 years) were included in this study. Thirty-one patients received EBP that targeted CSF leak segments, and 25 received a blind EBP because primary CSF leak sites were not identified (19 patients via a lumbar epidural route, mainly the L 3-4 level, regardless of primary CSF leak site, and 6 patients via upper thoracic epidural spaces, mainly the T4-6 level). In the 31 patients who received a targeted EBP, 27 (87.1%) exhibited clinical improvement after first administration. In contrast, 13 of the 25 patients (52%) who received a blind EBP via a lumbar or upper thoracic epidural route achieved complete recovery. Targeted EBPs were more effective than blind EBPs for the treatment of SIH (p < 0.05). EBPs targeting CSF leaks can be safely placed under fluoroscopic guidance in patients with SIH and are more likely to be effective than blindly placed EBPs.