Botulinum toxin type A (BTX-A) represents the gold standard therapy for focal spasticity after stroke, with low prevalence of complications, reversibility, and efficacy in reducing spastic hypertonia. Current guidelines suggest the employment of a dosage up to 600 units (U) of BTX-A to treat spasticity after stroke, to avoid important adverse effects and the development of antibodies against the neurotoxin. In recent years, NT 201, a new BTX-A free of complexing proteins, has been used for treating several movement disorders, showing safety and efficacy in upper limb spasticity. In a prospective, non-randomized, open-label study, we studied the efficacy and safety of higher doses of BTX-A NT 201 (up to 840 U) in 25 consecutive patients with upper and lower limb spasticity after stroke, evaluated at 30 and 90 days after injections. Before and after the treatment, the grade of spasticity, the disability, and spasticity-related pain were extensively measured. After 30 days of follow-up, a great reduction of spasticity and pain with improvement of disability was observed. The effects were still present at 90 days of follow-up. No major adverse events were observed. Higher doses of BTX-A NT 201 appeared to be safe and efficacious in patients with upper and lower limb spasticity after stroke. However, further investigations are needed to determine its reproducibility in larger case series or randomized clinical trials and to observe the absence of antibodies against the neurotoxin also after repeated injections.