OBJECTIVES: Less than 10% of patients admitted to the ICU develop severe distributive shock (DS), which carries substantial mortality and economic burden under current treatment. Giapreza represents the addition of a 3^rd mechanism to the treatment paradigm for DS. This analysis estimated the budget impact of adding Ang2 to background therapy (SOC) for severe DS in US hospitals. METHODS: We developed a budget impact model based on ATHOS-3 clinical trial results. The base-case assumes a hospital with 77 ICU beds and a one-year time horizon. The proportion of ICU patients treated for severe DS was based on published literature and MIMIC-III. Per ATHOS-3, Giapreza reduces use of other vasopressors. Adverse event and hospital length of stay (LOS) rates were drawn from ATHOS-3. Vasopressor costs were derived from current wholesale acquisition prices. LOS costs were drawn from the literature. Drug rebates and discounting of future costs were not considered. Sensitivity analyses were conducted. RESULTS: In a hypothetical US hospital with 77 ICU beds, the number of severe DS patients treated with vasopressors was estimated to be 188 per year. The average cost for treated ICU patients was estimated at $6,828,199-$6,847,001 for Giapreza + SOC ($126,181-$144,983 for medications; $6,702,018 for hospital stay) and $6,765,957for SOC alone, with a net budget impact of $62,242-$87,043. Higher costs for Giapreza are due to the higher probability of survival (54 vs. 46%) resulting in longer hospital stays. Sensitivity analyses showed that number of severe DS patients, Giapreza uptake, and Giapreza price were primary drivers of total costs; results were robust within values tested. CONCLUSIONS: Use of Giapreza is associated with higher total costs per patient, driven primarily by survival-associated resource use. Costs of managing adverse events are lower with Giapreza when compared to the current standard of care.