Digital ischemia following extracorporeal membrane oxygenation (ECMO) therapy is a known complication with potential devastating long-term sequela. Onabotulinum toxin type A (BTX-A) has been demonstrated to be effective for digital ischemia in adults with Raynaud’s phenomenon. The objective of this study is to describe the use of BTX-A in pediatric and neonatal patients with digital ischemia following ECMO therapy. Three consecutive patients with digital ischemia after ECMO therapy were included. Patient ages ranged from 3 days to 13 months. Twenty-five to 50 units of BTX-A were injected to each affected extremity targeting the areas around the known arterial anatomy of the hands and feet. On post-injection day one, all patients demonstrated improvement in ischemic discoloration. Complete resolution was noted by treatment day 3 in one case and near complete resolution by day 16 in the second. Case 3 expired on hospital day four from an unrelated intracranial hemorrhage. No complications or digital loss were observed. Onabotulinum toxin type A as an off-label treatment for digital ischemia was demonstrated to be safe and effective in pediatric and neonatal patients. Clinical improvement was noted in all patients by post-procedure day one, with two patients demonstrating near to complete resolution within 3 weeks.