Objectives To compare the clinical characteristics and the long-term outcome of a large series of patients with blepharospasm (BS) treated with the two most used brands of BoNT-A over the last 15 years. Methods We have reviewed the clinical charts of 128 patients with BS who received botulinum neurotoxin (BoNT) in 1341 treatments (Botox in 1009, Dysport in 332) over the last 15 years. Results Mean dose per session was 34U ± 15 for Botox and 152U ± 54 for Dysport. Mean latency of clinical effect was 4.5 ± 4.6 days for Botox and 5.0 ± 5.7 days for Dysport (P > 0.05). Mean duration of clinical improvement was higher for Dysport than Botox: 80.1 ± 36.3 and 66.2 ± 39.8 days, respectively (P < 0.01). In a six-point scale (0: no efficacy, 6: remission of BS), the mean efficacy of both treatments was 3.60 ± 1.3; 3.51 ± 1.4 (Botox) and 3.85 ± 1.2 (Dysport), P < 0.01. The doses of Botox (β = 0.40) and Dysport (β = 0.16) were significantly increased over time. Side effects occurred in 325 out of 1341 treatments (24.2%): 21.8% of the patients who had received Botox, and in 31.6% of those who had received Dysport (P < 0.01). Conclusions Both brands are effective and safe in treating blepharospasm; efficacy is long lasting. The differences in outcome and side effects suggest that, albeit the active drug is the same, Botox and Dysport should be considered as two different drugs.