ABSTRACT: Our objectives were to determine the incidence of critical illness–related corticosteroid insufficiency (CIRCI) in patients with septic shock using a 1 μg corticotropin (ACTH) test and to describe their clinical outcomes. We retrospectively identified 219 consecutive patients with septic shock assessed for CIRCI with a 1 μg ACTH test. Standardized testing involved plasma cortisol measurements at baseline (T0) and at 30 min (T30) and 60 min (T60) after ACTH administration. The maximal increase in cortisol (Δ max) was calculated as the difference between T0 and the highest cortisol value at T30 or T60. Critical illness–related corticosteroid insufficiency was defined as Δ max less than 9 μg/dL after ACTH administration. The mean age of the cohort was 63.0 ± 15.8 years, mean Acute Physiology and Chronic Health Evaluation II score was 26.3 ± 8.1, 85.6% were mechanically ventilated, and the mean number of organ failures was 3.0 ± 1.2. Critical illness–related corticosteroid insufficiency was diagnosed in 70.8% of patients. Twenty-eight-day mortality was highest in patients with baseline cortisol greater than 65 μg/dL (62.5%) and in those with baseline cortisol 34 μg/dL or greater and Δ max less than 9 μg/dL (50.0%). There was no difference in mortality in patients with and without CIRCI (53.9% vs. 36.4%, P = 0.08). Corticosteroids were administered to 69.4% of patients for 5.3 ± 3.6 days. For patients with CIRCI, intensive care unit mortality was similar for those who received corticosteroids compared with those who did not (46.0% vs. 25.0%, P = 0.166). The incidence of CIRCI based on 1 μg ACTH was high in this septic shock cohort. The highest mortality rates were observed in patients with high baseline cortisol and in those who failed to respond appropriately to ACTH. The administration of corticosteroids was not associated with a reduction in mortality.