Sialorrhea is frequent and invalidating in patients with amyotrophic lateral sclerosis (ALS) or Parkinson's disease (PD). Botulinum toxin (BTX) emerged as an alternative to traditional treatments. We evaluated efficacy and tolerability of ultrasound-guided BTX-B injections in parotids and submandibular glands in 18 patients with ALS or PD. At 1 week, both objective (cotton rolls weight) and subjective evaluations (dedicated clinical scales) documented sialorrhea reduction (p<0.01). ALS patients reported shorter benefit duration (p<0.001) and higher prevalence of viscous saliva (seven vs one patients), possibly due to different pattern of autonomic involvement. BTX-B seems efficacious in reducing sialorrhea in ALS and PD but the risk-benefit ratio might differ between these two conditions. This might have implications for clinical practice.