Objectives: This study attempted to prospectively validate a modified Thrombolysis In Myocardial Infarction (TIMI) risk score that classifies patients with either ST-segment deviation or cardiac troponin elevation as high risk. The objectives were to determine the ability of the modified score to risk-stratify emergency department (ED) patients with chest pain and to identify patients safe for early discharge. Methods: This was a prospective cohort study in an urban academic ED over a 9-month period. Patients over 24 years of age with a primary complaint of chest pain were enrolled. On-duty physicians completed standardized data collection forms prior to diagnostic testing. Cardiac troponin T-values of >99th percentile (≥0.01 ng/mL) were considered elevated. The primary outcome was acute myocardial infarction (AMI), revascularization, or death within 30 days. The overall diagnostic accuracy of the risk scores was compared by generating receiver operating characteristic (ROC) curves and comparing the area under the curve. The performance of the risk scores at potential decision thresholds was assessed by calculating the sensitivity and specificity at each potential cut-point. Results: The study enrolled 1,017 patients with the following characteristics: mean (±SD) age 59.3 (±13.8) years, 60.6% male, 17.9% with a history of diabetes, and 22.4% with a history of myocardial infarction. A total of 117 (11.5%) experienced a cardiac event within 30 days (6.6% AMI, 8.9% revascularization, 0.2% death of cardiac or unknown cause). The modified TIMI risk score outperformed the original with regard to overall diagnostic accuracy (area under the ROC curve = 0.83 vs. 0.79; p = 0.030; absolute difference 0.037; 95% confidence interval [CI] = 0.004 to 0.071). The specificity of the modified score was lower at all cut-points of >0. Sensitivity and specificity at potential decision thresholds were: >0 = sensitivity 96.6%, specificity 23.7%; >1 = sensitivity 91.5%, specificity 54.2%; and >2 = sensitivity 80.3%, specificity 73.4%. The lowest cut-point (TIMI/modified TIMI >0) was the only cut-point to predict cardiac events with sufficient sensitivity to consider early discharge. The sensitivity and specificity of the modified and original TIMI risk scores at this cut-point were identical. Conclusions: The modified TIMI risk score outperformed the original with regard to overall diagnostic accuracy. However, it had lower specificity at all cut-points of >0, suggesting suboptimal risk stratification in high-risk patients. It also lacked sufficient sensitivity and specificity to safely guide patient disposition. Both scores are insufficiently sensitive and specific to recommend as the sole means of determining disposition in ED chest pain patients. © 2010 by the Society for Academic Emergency Medicine.