Background and objectives The gold standard for the treatment of postdural puncture headache (PDPH) is the epidural blood patch (EBP). Regional techniques—sphenopalatine ganglion block (SPGB), greater occipital nerve block (GONB) and trigger point infiltration (TPI)—can also be used for the treatment of PDPH. Our objective was to evaluate the efficacy of these peripheral nerve blocks (PNBs) in the treatment of PDPH. Methods A retrospective study was conducted including all patients with PDPH in the obstetrics department of our institution between April 2016 and December 2017. Data were retrieved from clinical records regarding anesthetic technique, symptoms, treatment, Numeric Pain Score (NPS) before and after treatment, among others. Results We observed 50 cases of PDPH: 25 following spinal anesthesia, 19 following epidural block and 6 following combined spinal-epidural. Of these, seven were managed conservatively and one received EBP as first-line treatment. The remaining 42 patients received PNB as first-line treatment. Of these, 27 received only 1 course of PNB, while 15 received 2 courses. We observed a statistically significant improvement in the NPS after the first course of blocks (n=42), with a reduction of the median NPS by 6.0 (IQR 4.0–7.5; p<0.001). Improvement was also observed after the second course of blocks (n=15), with a reduction of the median NPS of 3.5 (IQR 1.5–5.0; p=0.02). Due to treatment failure, 9 of the 42 patients treated with PNB required EBP. None of these were cases following spinal anesthesia. Conclusion SPGB, GONB and TPI can be safe and effective options for treatment of PDPH, but do not completely eliminate the need for EBP. Prospective studies designed to identify factors associated with unsuccessful treatment are required.