Background: Postdural puncture headache (PDPH) is one of the earliest recognized complications of regional anesthesia. It is a common complication after inadvertent dural puncture. When conservative management is ineffective, the Epidural Blood Patch (EBP) is the “gold standard” for the treatment of PDPH. Due to the potential complications of EBP, several alternatives have been promoted as peripheral nerve blocks.A systematic review of the use of regional anesthesia for PDPH is needed to identify an alternative method of pain management.Objectives: To systematically review literature to establish the efficacy and applicability of regional anesthesia used in the treatment of PDPH in the hospital setting.Methods: Embase, MEDLINE, Google Scholar and Cochrane Central Trials Register were systematically searched in May 2020 for studies examining regional anesthesia for PDPH. The methodological quality of the studies and their results were appraised using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and specific measurement properties criteria, respectively.Results: Nineteen studies evaluating peripheral nerve blocks for PDPH were included for a total of 221 patients. Sphenopalatine ganglion block (SPGB), greater occipital nerve block (GONB) and lesser occipital nerve block (LONB) were performed. All participants reported NRS lower than 4 after peripheral nerve blocks at 1, 24 and 48 hours. Only patients who experienced PDPH after diagnostic lumbar puncture reported NRS ≥ 4 after 48 hours. No adverse event was reported after the execution of nerve blocks, except an occasionally discomfort related to the insertion of cotton-tip applicators intranasally for SPGB. 17% of patients underwent a second or more peripheral nerve block due to uncontrolled pain. In 30 participants, EBP was required; none of cases followed spinal anesthesia.Conclusion: Peripheral nerve blocks can be considered as analgesic options in the management of PDPH, as not all cases require EBP for successful treatment. Treatment of PDPH with peripheral nerve blocks seems to be a minimal invasive, easy and effective method, which can offer to patients when conservative management is ineffective.