Persistent occipital neuralgia can produce severe headaches that are difficult to control by conservative or surgical approaches. We retrospectively describe a series of six patients with severe occipital neuralgia who received conservative and interventional therapies, including oral antidepressants, membrane stabilizers, opioids, and traditional occipital nerve blocks without significant relief. This group then underwent occipital nerve blocks using the botulinum toxin type A (BoNT-A) BOTOX Type A (Allergan, Inc., Irvine, CA, U.S.A.) 50 U for each block (100 U if bilateral). Significant decreases in pain Visual Analog Scale (VAS) scores and improvement in Pain Disability Index (PDI) were observed at four weeks follow-up in five out of six patients following BoNT-A occipital nerve block. The mean VAS score changed from 8 +/- 1.8 (median score of 8.5) to 2 +/- 2.7 (median score of 1), while PDI improved from 51.5 +/- 17.6 (median 56) to 19.5 +/- 21 (median 17.5) and the duration of the pain relief increased to an average of 16.3 +/- 3.2 weeks (median 16) from an average of 1.9 +/- 0.5 weeks (median 2) compared to diagnostic 0.5% bupivacaine block. Following block resolution, the average pain scores and PDI returned to similar levels as before BoNT-A block. In conclusion, BoNT-A occipital nerve blocks provided a much longer duration of analgesia than diagnostic local anesthetics. The functional capacity improvement measured by PDI was profound enough in the majority of the patients to allow patients to resume their regular daily activities for a period of time.