Introduction: Chest pain and symptoms of acute coronary syndrome are responsible for a large proportion of ED visits and acute hospitalizations. However, only about 15% of patients presenting to the ED with high-risk symptoms do, in fact, have an acute coronary syndrome. The objective of this study is to derive a 2-hour high-sensitivity Troponin T (hsTnT) testing algorithm with outcome based-cutoffs to rapidly rule out acute myocardial infarction (AMI) in a large proportion of ED chest pain patients. Methods: Patients included consecutive ED patients with a chief complaint of cardiac chest pain who had an hsTnT assay performed at ED arrival and 2 hours after ED arrival. Administrative databases were queried to identify troponin results and major adverse cardiac outcomes (MACE) including death, MI, and revascularization. Test characteristics of iterative combinations of initial troponin level and absolute change in troponin level were quantified in order to identify the testing algorithm that identified the greatest proportion of patients eligible for early discharge while maintaining a target sensitivity of 98.5% for the primary outcome of 7-day AMI. Results: 755 eligible patients had hsTnT assays performed at ED arrival and at 2 hours. 91 patients (12.1%) had a 7-day AMI while 108 (14.0%) had 7-day MACE. An initial hsTnT level of less than 14 ng/L, in combination with a 2-hour absolute change of less than 10ng/L had a sensitivity of 98.9% (95% CI 94.0,99.8) and an NPV of 99.8% (95% CI 98.7, 100.0) for 7-day AMI. This identified 58.5% of all patients as being suitable for early discharge. Sensitivity and NPV for 7-day MACE were 90.0% (95% CI 83.3, 94.2) and 97.3% (95% CI 95.3,98.4) respectively. Sex-specific differences in test characteristics were not clinically important. Rule-in hsTnT cutoffs were also evaluated, with specificities ranging from 85-95%, although cutoffs with higher specificity had less ability to rapidly rule-in AMI, leaving more patients with indeterminate results after 2 hours. Conclusion: A hsTnT algorithm can safely and accurately rule out AMI in 58.5% of ED chest pain patients within 2 hours of ED arrival. The lower sensitivity of this algorithm for MACE compared to AMI speaks to the importance of clinical assessment and ECG findings in identifying patients at risk for acute coronary syndromes.