Introduction: We aimed to determine the effect of different botulinum toxin‐A (BTX‐A) dilutions on the treatment efficacy and side effects for amyotrophic lateral sclerosis (ALS) related sialorrhea. Methods: Ten patients were enrolled in the study. BTX‐A dilution for Group A was 100 U in 1 ml of saline, whereas the dilution for Group B was 100 U in 2 ml of saline. Both groups received 20 U of BTX‐A in each parotid gland, and assessments were made by means of the Drooling Impact Scale, items 1 and 3 of the ALS functional rating scale, and visual analog scales for drooling and swallowing function. Results: Although both groups exhibited a similar improvement in drooling, Group B had a mild but significant deterioration in bulbar function that was not evident in Group A. Conclusions: These results suggest that BTX‐A has a safer profile when reconstituted with 1 ml instead of 2 ml of saline. Muscle Nerve, 2013