Inclusion Criteria:

• Patients diagnosed with sepsis within 24 hours of meeting all of the following criteria will be eligible to participate in the study:
• * Sepsis-3 criteria: acute hospital admission for suspected infection with new or worsening organ dysfunction measured by the increase in Sequential Organ failure Assessment (SOFA) score of 2 points or more.
• * IV vasopressor use or persistent hypotension (MAP \< 65 mm Hg) after initial fluid resuscitation in the ED or ICU (30 mL/kg unless deemed excessive by the treating clinician).

Exclusion Criteria:

• * High-dose vasopressors (norepinephrine equivalent \> 0.3 µg/kg/min).
• * Inadequately controlled source of infection.
• * Cardiogenic or obstructive (massive pulmonary embolism) shock.
• * Clinical suspicion or confirmed diagnosis of bowel obstruction, bowel ischemia, or ileus.
• * Contraindication to enteral intake (ileus, vomiting, gastrointestinal bleeding, endoscopic procedures etc.).
• * Recent myocardial infarction (within the past 3 months).
• * Recent treatment for peripheral vascular disease (within the past 3 months).
• * Current use of monoamine oxidase inhibitors.
• * Recent stroke (within the past 3 months).
• * Prior use of midodrine as a home medication.
• * Known allergy to midodrine.
• * Comfort care measures.
• * Pregnancy.
• * Fludrocortisone acetate as a current home medication.
• * Bradycardia (heart rate \< 50 beats/min).
• * Untreated pheochromocytoma.
• * Untreated thyrotoxicosis.
• * Open-angle glaucoma.
• * Treating emergency or critical care physician unwilling to enroll patient in trial.
• * Inability to give consent for participation and no representative or surrogate available to consent.