Introduction: Botulinum toxin is the medical therapy of choice in HSF. However, in some patients, especially those with a long history of HFS and extensive spasms, the therapeutic effect of botulinum toxin is insufficient, due to a small therapeutic window associated with side-effects or recurring spasms. I report the cases of two patients with HSF who responded favourably to the therapeutic combination of pregabalin and botulinum toxin. Patients: Both patients had a longstanding history of HFS and were treated with botulinum toxin over a period of several years. In the last two years of therapy the facial spasms also involved the perioral muscles and were never sufficiently relieved by botulinum toxin, due to the fact that higher doses of the substance lead to adverse effects. Both patinets declined to undergo a neurosurgical intervention. The EDB test showed a decrease in the CMAP amplitude of >60 percent. Without changing the botulinum toxin regime, pregabalin up to 150mg twice daily was added for a 1-month trial period. The HFS subsided gradually over a 3-week period. After discontinuation of the drug at the end of the trial period, the symptoms recurred after ~4 weeks. Rechallange with pregabalin alone at a dosage of 300mg/d over 4 weeks improved HSF but did not prevent the development of spasms. Botulinum toxin therapy was therefore resumed, while pregabalin treatment was continued in parallel. The spasms began to disappear after approximately one week using the combination therapy. Discussion: Gabapentin and pregabalin are known to bind to the α2δ-subunit of the voltage-dependent calcium channels, which are also present in the facial nerve. Furthermore, pregabalin has been shown to have a higher affinity to the calcium channels compared to gabapentin. Following the administration of botulinum toxin alone, both patients of the present study continued to develop spasms over a treatment period of at least one year. Only after the combined treatment with pregabalin and botulinum toxin, the complete and sustained cessation of HSF was achieved. The therapy with pregabalin alone alleviated the spasms, but did not prevent their occurrence. Therefore, we recommend pregabalin as a supplementary treatment option in those patients with facial spasms which can not be relieved sufficiently by botulinum toxin alone.