© 2018 American College of Cardiology Foundation Background: Both the modified History, Electrocardiogram, Age, Risk factors and Troponin (HEART) score and the Emergency Department Assessment of Chest pain Score (EDACS) can identify patients with possible acute coronary syndrome (ACS) at low risk (<1%) for major adverse cardiac events (MACE). Objectives: The authors sought to assess the comparative accuracy of the EDACS (original and simplified) and modified HEART risk scores when using cardiac troponin I (cTnI) cutoffs below the 99th percentile, and obtain precise MACE risk estimates. Methods: The authors conducted a retrospective study of adult emergency department (ED) patients evaluated for possible ACS in an integrated health care system between 2013 and 2015. Negative predictive values for MACE (composite of myocardial infarction, cardiogenic shock, cardiac arrest, and all-cause mortality) were determined at 60 days. Reclassification analyses were used to assess the comparative accuracy of risk scores and lower cTnI cutoffs. Results: A total of 118,822 patients with possible ACS were included. The 3 risk scores’ accuracies were optimized using the lower limit of cTnI quantitation (<0.02 ng/ml) to define low risk for 60-day MACE, with reclassification yields ranging between 3.4% and 3.9%, while maintaining similar negative predictive values (range 99.49% to 99.55%; p = 0.27). The original EDACS identified the largest proportion of patients as low risk (60.6%; p < 0.0001). Conclusions: Among ED patients with possible ACS, the modified HEART score, original EDACS, and simplified EDACS all predicted a low risk of 60-day MACE with improved accuracy using a cTnI cutoff below the 99th percentile. The original EDACS identified the most low-risk patients, and thus may be the preferred risk score.