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Introduction: Prolonged use of intravenous (IV) vasopressors in critically ill patients increases the risk of ischemic complications, arrhythmias, and catheter-associated infections. Droxidopa, an oral norepinephrine precursor, has gained attention as an off-label adjunct to facilitate vasopressor weaning in the ICU. Despite growing clinical use, the evidence supporting its safety and efficacy in critically ill populations has not been systematically reviewed. Methods: A systematic review was conducted following PRISMA guidelines. Eligible studies included retrospective cohorts, case series, and abstracts reporting primary clinical data on droxidopa use in ICU patients. Outcomes of interest included time to vasopressor discontinuation, droxidopa duration, ICU length of stay (LOS), and ICU mortality. Risk of bias was assessed using ROBINS-I and the JBI Critical Appraisal Checklist. Results: Seven studies comprising 161 ICU patients met inclusion criteria. Median time to vasopressor discontinuation ranged from 29 to 120 hours. Duration of droxidopa use ranged from 87 to 192 hours. ICU LOS was reported in two studies (18–44 days); ICU mortality was inconsistently documented. Most studies reported successful vasopressor discontinuation, though variation in dosing, timing, and reporting limited comparability. Conclusions: Droxidopa may assist in vasopressor weaning in ICU patients, but available evidence remains limited and heterogeneous. Further research is warranted.