The potential clinical utility of the Duke Treadmill Score (DTS) in the Emergency Department (ED) to risk-stratify patients with chest pain but negative cardiac biomarkers and non-diagnostic electrocardiograms is unclear. We evaluated whether DTS was associated with 30-day adverse cardiac outcomes for low-risk ED patients with chest pain. For this prospective, observational cohort study, the primary outcome was any of the following at 30 days: cardiac death, myocardial infarction, or coronary revascularization. DTS risk categories (low, intermediate, high) were compared with 30-day cardiac outcomes. We enrolled 191 patients, of whom 20 (10%) were lost to follow-up, leaving 171 patients (mean age 53.3 +/- 12.4 years, 54% female, 3.5% adverse event rate) for evaluation. Sensitivity and specificity of DTS for 30-day events were 83.3% and 71.5%, respectively, with a 99.2% negative predictive value (confidence interval 95.4-99.9) for 30-day event-free survival. In this cohort of low-risk ED patients with chest pain, DTS demonstrated excellent negative predictive value for 30-day event-free survival and facilitated safe disposition of a large subset of patients.