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The term "single-sample rule-out" refers to the ability of very low concentrations of high-sensitivity cardiac troponin (hs-cTn) on presentation to exclude acute myocardial infarction with high clinical sensitivity and negative predictive value. Observational and randomized studies have confirmed this ability. Some guidelines endorse use of a concentration of hs-cTn at the assay's limit of detection, while other studies have validated the use of higher concentrations, allowing this approach to identify a greater proportion of patients at low risk. In most studies, at least 30% of patients can be triaged with this approach. The concentration of hs-cTn varies according to the assay used and sometimes how regulations permit reporting. It is clear that patients need to be at least 2 hours from the onset of symptoms being evaluated. Caution is warranted, particularly with older patients, women, and patients with underlying cardiac comorbidities. [Display omitted] • Rapid, safe, and accurate exclusion of acute myocardial infarction can facilitate triage of patients in the emergency department. • Observational and randomized studies have found that a single low assay-dependent, hs-cTn measurement taken >2 hours after symptom onset in a patient with a nonischemic electrocardiogram can effectively exclude acute MI. • Additional studies are needed to assess the utility of this approach in patients undergoing evaluation earlier after the onset of symptoms and to establish optimum blood level thresholds for women and patients with specific comorbidities. [ABSTRACT FROM AUTHOR]