Introduction: Age and systolic blood pressure (SBP) are important predictors of Acute Cerebrovascular Syndrome (ACVS). Yet, the effect of SBP is confounded by age, making its independent contribution to ACVS risk difficult to quantify. Here we use logistic regression to explore the role of SBP in younger and older ED patients. Methods: Data comprised 1019 ED patients (ACVS 70%, 30% non-ACVS) enrolled during a 28-month period of an ongoing prospective, observational, multi-site stroke biomarker study (SpecTRA). We used logistic regression to examine the effects of age, sex, and the age:SBP interaction as predictive markers of the diagnosis of ACVS. Results: Participants (53% male) ranged in age from 18 to 97 years (Q1=58, median=70, Q3=80). SBP ranged from 84 to 248 mmHg (Q1=137, median=154, Q3=174). In our initial regression model, age, sex, SBP and the age:SBP interaction were all significant (p<0.01). Using cubic regression splines for age, sbp and their interaction yields the same conclusion (p<0.01). To better understand the role of SBP in younger vs. older patients, we stratified the sample at the median age (70 years of age). In the younger group (n=510), participants were 55% male, 60% ACVS, and had SBP ranging from 91 to 236 mmHg (Q1=133, median=148, Q3=165). In the older group (n=509), participants were 51% male, 82% ACVS and had SBP ranging from 84 to 248 mmHg (Q1=143, median=159, Q3=179), a shift of approximately 10 mmHg between the groups. The logistic regression model was then fit separately to each group without the age:SBP interaction term. In the younger group, we found SBP to be highly significant (p<0.001), with an odds-ratio (OR) of 1.18 per 10 mmHg (95% CI: 1.10-1.29). In the older group, we found that SBP was not significant (p=0.91), with an OR of 1.00 per 10 mmHg (95% CI: 0.91-1.08). Age and sex were also significant risk factors in the younger group (each p<0.01), though not in the older group (both p>0.07). Conclusion: Our findings suggest that for ED patients suspected of ACVS, SBP is a clinically relevant predictor for younger patients, with higher SBP associated with an increased risk of ACVS, regardless of patient age and sex. SBP does not appear to be a strong predictor for patients over 70. ED physicians can leverage this finding by attributing greater importance to elevated SBP in younger patients than older patients when working toward a clinical suspicion of ACVS.