Background: Sialorrhea is associated with various neurological conditions. Among critically ill patients with acute neurological injuries (ANI), sialorrhea leads to several adverse consequences, including extubation failure, inability to initiate non-invasive ventilation, aspiration pneumonia and prolonged hospitalization. Botulinum toxin (BoTN) injections can reduce salivary production. Both BoTN-A and BoTN-B are effective in managing sialorrhea among patients with neurogenic dysphagia. BoTN utilization for sialorrhea in critically ill adult ANI patients is not well-studied. Purpose: The purpose of this study to evaluate the safety and feasibility of using BoTN-A salivary injections to reduce sialorrhea in ANI patients. Research Design: In this case series, we retrospectively reviewed the off-label use of BoTN-A for sialorrhea in ANI patients at the University of North Carolina Neurosciences Intensive Care Unit. Study Sample: Six patients with ANI who received BoTNA treatment for neurogenic sialorrhea in absence of infection and medications with known side-effect of sialorrhea. Data Collection: For safety evaluation, we reviewed any documented adverse effects of BoTN-A injection. For efficacy, we evaluated the drooling severity, suctioning frequency, oxygen requirements, continued days on the ventilator, and pneumonia diagnoses. Results: All patients had reduction in their documented drooling and suctioning requirements following BoTN-A injection. None had adverse events associated with BoTN-A injections. All patients experienced recurrent ventilator-associated pneumonias prior to BoTN-A injections whereas four patients had no pneumonia events after injections. Also, two patients were successfully weaned of oxygenation prior to discharge. Conclusions: This case series highlights the safety and potential efficacy of salivary gland BoTN-A for reducing refractory sialorrhea among critically ill ANI patients. Future studies are needed to evaluate whether sialorrhea reduction can lead to reduced hospital complications and overall length of hospital stay.