BACKGROUND AND PURPOSE—: Implementation of nurse-initiated protocols to manage fever, hyperglycemia, and swallowing dysfunction decreased death and disability 90 days poststroke in the QASC trial (Quality in Acute Stroke Care) conducted in 19 Australian acute stroke units (2005–2010). We now examine long-term all-cause mortality. METHODS—: Mortality was ascertained using Australia’s National Death Index. Cox proportional hazards regression compared time to death adjusting for correlation within stroke units using the cluster sandwich (Huber–White estimator) method. Primary analyses included treatment group only unadjusted for covariates. Secondary analysis adjusted for age, sex, marital status, education, and stroke severity using multiple imputation for missing covariates. RESULTS—: One thousand and seventy-six participants (intervention n=600; control n=476) were followed for a median of 4.1 years (minimum 0.3 to maximum 70 months), of whom 264 (24.5%) had died. Baseline demographic and clinical characteristics were generally well balanced by group. The QASC intervention group had improved long-term survival (>20%), but this was only statistically significant in adjusted analyses (unadjusted hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.58–1.07; P=0.13; adjusted HR, 0.77; 95% CI, 0.59–0.99; P=0.045). Older age (75–84 years; HR, 4.9; 95% CI, 2.8–8.7; P<0.001) and increasing stroke severity (HR, 1.5; 95% CI, 1.3–1.9; P<0.001) were associated with increased mortality, while being married (HR, 0.70; 95% CI, 0.49–0.99; P=0.042) was associated with increased likelihood of survival. Cardiovascular disease (including stroke) was listed either as the primary or secondary cause of death in 80% (211/264) of all deaths. CONCLUSIONS—: Our results demonstrate the potential long-term and sustained benefit of nurse-initiated multidisciplinary protocols for management of fever, hyperglycemia, and swallowing dysfunction. These protocols should be a routine part of acute stroke care. CLINICAL TRIAL REGISTRATION—: URL: http://www.anzctr.org.au. Unique identifier: ACTRN12608000563369.