Injectable botulinum neurotoxin (BoNT) is the principal effective treatment for blepharospasm (BSP). This trial explores the safety and efficacy of topical acetyl hexapeptide-8 (AH8), a competitive SNAP25 inhibitor, as a potential new therapy in BSP. Double-blind, placebo-controlled, randomized trial of daily topical application of AH8 in 24 patients with BSP. The primary outcome was time to return to baseline Jankovic Blepharospasm Rating Scale (JBRS) after a BoNT injection simultaneously with the initiation of AH8. Patients displaying a strictly regular pattern of response to 3-monthly injections of BoNT were included. There were no significant adverse events. There was a trend for longer time until return to baseline JBRS after injection in the active group compared to placebo (3.7 months vs. 3.0 months), and for better scores in the active group. One-third (4/12) of the patients in the active group had a considerable extension of symptom control after BoNT (range: 3.3-7.1 months). Topical AH8 is safe and promising for extending the duration of action of BoNT therapy for BSP.