OBJECTIVES: Distributive shock (DS) is characterized by peripheral vasodilation and reduced blood pressure despite adequate cardiac output. Patients with DS unresponsive to currently available vasopressors are at high 30-day mortality risk. Current vasopressors are also associated with significant side effects. In the ATHOS-3 Phase 3 clinical trial, addition of Giapreza to current vasopressors (SOC) was shown to increase mean arterial blood pressure (MAP) and was associated with reduced 28-day mortality in ICU patients with refractory vasodilatory shock (54% vs. 46%). The objective of this analysis is to determine the cost-effectiveness of adding Giapreza to SOC for DS in the ICU for US hospitals. METHODS: A decision-analytic model was developed using the results of the ATHOS-3 trial, using the perspective of a US hospital system. Short-term mortality outcomes were based on 28-day ATHOS-3 survival rates. Lifetime projections were modeled using individually estimated life expectancies for 28-day survivors. Health state utilities were modeled using estimates for the US adult population weighted for sepsis mortality. Resource use rates were based on the clinical trial. Resource use cost was drawn from the literature and were inflated to 2017 dollars. QALYs were discounted at 3%. Sub-groups included MAP levels, prior vasopressin use, and those <65 vs. 65+ years old. Sensitivity analyses assessed model uncertainty. RESULTS: The base-case cost-effectiveness analyses showed an increase in survival of 0.08 lives saved with the addition of Giapreza, for an estimated $85,044 - $110,734 per life-saved. The long-term results showed an increase in quality-adjusted survival of 0.57 QALYs, with a cost of $11,576 4/QALY - $15,072/QALY. Sensitivity analyses showed that mortality, Giapreza cost, and resource use cost were primary drivers of long-term results and that the all results were robust within values tested. CONCLUSIONS: The addition of Giapreza to background treatment in refractory DS in the ICU setting is cost-effective.