The invention provides decision tree based systems and methods for estimating the risk of acute coronary syndrome (ACS) in subjects suspect of having ACS. In particular, systems and methods are provided that employ additive decision tree based algorithms to process a subject's initial cardiac troponin I or T (cTnI or cTnT) concentration, a subject's cTnI or cTnT rate of change, and at least one of the following: the subject's age, the subject's gender, the subject's ECG value, the subject's hematology parameter value, to generate an estimate risk of ACS. Such risk stratification allows, for example, patients to be ruled in or rule out with regard to needing urgent treatment.