Background: Cerebrovascular disease often coexists with coronary artery disease (CAD), and it has been associated with worse clinical outcomes in CAD patients. However, the prognostic effect of prior stroke on long-term outcomes in patients with acute coronary syndrome (ACS) is still unclear.Methods and Results: An observational cohort study of ACS patients who underwent emergency percutaneous coronary intervention (PCI) between January 1999 and May 2015 was conducted. Patients were divided into 2 groups according to their history of stroke. We evaluated both all-cause death and cardiac death. Of the 2,548 consecutive ACS patients in the current cohort, 268 (10.5%) had a history of stroke at the onset of ACS. Patients with a history of stroke were older and had a higher prevalence of comorbidities such as hypertension or renal deficiency. The cumulative incidences of all-cause death and cardiac death were significantly higher in patients with a history of stroke (both log-rank P<0.0001). Multivariate Cox hazard regression analysis showed that a history of stroke was significantly associated with the incidences of all-cause death (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.20–1.85, P=0.0004) and cardiac death (HR 1.41, 95% CI 1.03–1.93, P=0.03).Conclusions: About 10% of the ACS patients had a history of stroke and had worse clinical outcomes.