Hypotension secondary to autonomic dysfunction is a common complication of acute spinal cord injury (SCI) that may worsen neurologic outcomes. Midodrine, an enteral α-1 agonist, is often used to facilitate weaning intravenous (IV) vasopressors, but its use can be limited by reflex bradycardia. Alternative enteral agents to facilitate this wean in the acute post-SCI setting have not been described. We aim to describe novel application of droxidopa, an enteral precursor of norepinephrine that is approved to treat neurogenic orthostatic hypotension, in the acute post-SCI setting. Droxidopa may be an alternative enteral therapy for those intolerant of midodrine due to reflex bradycardia. We describe two patients suffering traumatic cervical SCI who were successfully weaned off IV vasopressors with droxidopa after failing with midodrine. The first patient was a 64-year-old male who underwent C3–6 laminectomies and fusion after a ten-foot fall resulting in quadriparesis. Post-operatively, the addition of midodrine in an attempt to wean off IV vasopressors resulted in significant reflexive bradycardia. Treatment with droxidopa facilitated rapidly weaning IV vasopressors and transfer to a lower level of care within 72 hours of treatment initiation. The second patient was a 73-year-old male who underwent C3–5 laminectomies and fusion for a traumatic hyperflexion injury causing paraplegia. The addition of midodrine resulted in severe bradycardia, prompting consideration of pacemaker placement. However, with the addition of droxidopa, this was avoided, and the patient was weaned off IV vasopressors on dual oral therapy with midodrine and droxidopa. Droxidopa may be a viable enteral therapy to treat hypotension in patients after acute SCI who are otherwise not tolerating midodrine in order to wean off IV vasopressors. This strategy may avoid pacemaker placement and facilitate shorter stays in the intensive care unit, particularly for patients who are stable but require continued intensive care unit admission for IV vasopressors, which can be cost ineffective and human resource depleting.