Background and Purpose- More intensive secondary prevention with newer drugs may be cost-effective in patients with coronary artery disease (CAD). Whether some subgroups of patients who had a transient ischemic attack (TIA) or ischemic stroke, but no prior CAD are at similar high risk of myocardial infarction as those with prior CAD remains unclear. We determined whether the Essen score identified a subset of TIA/stroke patients without known prior CAD who, nevertheless, had a high risk of myocardial infarction on current secondary prevention management. Methods- In a population-based cohort (Oxford Vascular Study) of consecutive TIA or ischemic stroke patients recruited from 2002 to 2014, 10-year actuarial risks of myocardial infarction and of recurrent ischemic stroke were determined by face-to-face follow-up in patients with and without prior CAD using Kaplan-Meier analyses. Predictive value of the Essen score was assessed with C statistic. Results- Of 2555 patients with TIA/stroke (13 070 patient-years of follow-up), 10-year risk of myocardial infarction in those without prior CAD (n=2017, 78.9%) ranged from 0.9% (95% CI, 0-1.9) at Essen score ≤1 to 29.8% (95% CI, 7.7-46.6) in those with a score ≥5 (C statistic =0.64 [95% CI, 0.57-0.71] P<0.001). The score tended to be less predictive (difference: P=0.0460) for the risk of recurrent ischemic stroke (C statistic =0.57 [95% CI, 0.54-0.60]). Compared with patients with prior CAD (n=538, 21.1%), an Essen risk score of ≥4 (n=294, 11.5%) in those without prior CAD identified a subgroup at similar high 10-year risks of myocardial infarction (17.2% [95% CI, 6.9-26.3]; versus 16.9% [95% CI, 11.5-22.0]) and of recurrent stroke (40.4% [95% CI, 26.7-51.6]; versus 32.4% [95% CI, 25.2-38.8]). Conclusions- The Essen score is a simple clinical score to risk-stratify patients with TIA/stroke without prior CAD and to identify subsets who may be at sufficiently high risk of myocardial infarction and recurrent stroke to justify more intensive treatment or inclusion in trials.