Vasoactive therapy is often used to treat acute decompensated heart failure (ADHF). The authors sought to determine whether clinical outcomes are temporally associated with time to vasoactive therapy (vasoactive time) in ADHF. Using the Acute Decompensated Heart Failure (ADHERE) Registry, the authors examined the relationship between vasoactive time and inpatient mortality within 48 hours of hospitalization. Vasoactive agents were used early (defined as <6 hours) in 22,788 (63.8%) patients and late in 12,912 (36.2%). Median vasoactive time was 1.7 and 14.7 hours in the early and late groups, respectively. In-hospital mortality was significantly lower in the early group (odds ratio, 0.87; 95% confidence interval, 0.79–0.96; P=.006), and the adjusted odds of death increased 6.8% for every 6 hours of treatment delay (95% confidence interval, 4.2–9.6; P<.0001). Early vasoactive initiation is associated with improved outcomes in patients hospitalized for ADHF.