The Thrombolysis in Myocardial Infarction (TIMI) risk score is a 7-item tool derived from trials of patients with unstable angina/non-ST segment elevation myocardial infarction for risk stratification with respect to outcomes. It has been retrospectively evaluated in emergency department (ED) patients with potential acute coronary syndrome but has not been prospectively validated in this patient population. To validate the use of the TIMI risk score in the ED, we prospectively assess its potential utility in a broad ED chest pain patient population. This was a prospective observational cohort study of consecutive ED chest pain patients enrolled from July 2003 until October 2004. Data included demographics, medical and cardiac history, and components of the TIMI risk score. Investigators followed the hospital course daily for admitted patients, and 30-day follow-up was performed on hospitalized and discharged patients. The main outcome was death, acute myocardial infarction, or revascularization as stratified by TIMI risk score at 30 days. There were 1,481 eligible patient visits; 30-day follow-up was completed on 1,458 (98.4%) patients. Patients had mean age of 53.2+/-14 years and were 40% men, 66% black, and 30% white. Myocardial infarction occurred in 95 patients. The incidence of each TIMI risk factor was age greater than 65 years 21%, known coronary stenosis 18%, 3 or more risk factors 26%, ST-segment deviation 6%, 2 or more anginal events in the previous 24 hours 33%, aspirin use in the previous 7 days 35%, and elevated markers 6%. The incidence of 30-day death, acute myocardial infarction, and revascularization according to TIMI score is as follows: TIMI 0, 1.7% (95% confidence interval [CI] 0.42 to 2.95); TIMI 1, 8.2% (95% CI 5.27 to 11.04); TIMI 2, 8.6% (95% CI 5.02 to 12.08); TIMI 3, 16.8% (95% CI 10.91 to 22.62); TIMI 4, 24.6% (95% CI 16.38 to 32.77); TIMI 5, 37.5% (95% CI 21.25 to 53.75); and TIMI 6, 33.3% (95% CI 0 to 100). This relationship was highly significant. Among ED patients with chest pain, the TIMI risk score does correlate with outcome. However, in our study the TIMI risk score failed to stratify these patients into discrete groups according to risk score. Also, patients with the lowest risk as defined by a TIMI score of zero had a 1.7% incidence of adverse events. Therefore, the TIMI risk score should not be used in isolation to determine disposition of ED chest pain patients.