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IMPORTANCE AND OBJECTIVES:. This study assessed the potential advantages of treating hepatorenal syndrome-acute kidney injury (HRS-AKI) with terlipressin versus placebo in the ICU setting. DESIGN:. Patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days. SETTING:. A retrospective analysis of data from the phase III CONFIRM study. PARTICIPANTS:. Adult patients with HRS-AKI admitted to the ICU. MAIN OUTCOMES AND MEASURES:. In this substudy, we evaluated outcomes of the ICU stay and the need for organ support, including renal replacement therapy (RRT). RESULTS:. Among 300 patients with HRS-AKI from the CONFIRM study, 45 were treated in the ICU (terlipressin, 31/199 [16%]; placebo, 14/101 [14%]). On ICU admission, baseline demographics were similar across treatment arms, including severity of liver dysfunction. Among patients alive at the end of the ICU stay, those randomized to terlipressin had a significantly shorter median length of ICU stay than placebo (4 vs 11 d; p < 0.001). Terlipressin-treated patients had a significantly larger improvement in renal function from baseline versus placebo (–0.7 vs +0.2 mg/dL; p = 0.001), including when accounting for the interaction between treatment and day-of-patient-admission to the ICU (–0.7 vs +0.9 mg/dL; p < 0.001). Cumulative requirement for RRT through day 90 was improved in the terlipressin arm versus placebo (10/31 [32%] vs 8/14 [57%]; p = 0.12), although not significantly. Of 13 patients who received a liver transplant, five out of five (100%) in the placebo arm needed RRT through day 90 versus five out of eight (63%) in the terlipressin arm. CONCLUSIONS:. In this subanalysis of CONFIRM, patients admitted to the ICU with HRS-AKI who received terlipressin were more likely to achieve renal function improvement, based on serum creatinine changes by the end of treatment, and had significantly shorter lengths of ICU stay than patients randomized to the placebo arm.