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Objective: About one out of every 10 patients with chest pain in the emergency department (ED) are finally diagnosed with acute coronary syndrome (ACS). A HEART score of ≤ 3 has been shown to rule out ACS with a low risk of major adverse cardiac events (MACE) occurrence. It has been proposed that a negative CARE rule (≤1), which stands for the first four elements of the HEART score and excludes the troponin assay requirement, may have similar rule-out reliability. This study aimed to externally validate the CARE rule. Methods: In this multicenter, observational study a convenience sample consisting of patients over the age of 15 who had at least one troponin study were included. The performance of the CARE rule at the cut-off ≤1 for MACE prediction was assessed and compared to a HEART score of ≤3 and physicians’ gestalt. MACE was defined as myocardial infarction, coronary angioplasty, coronary artery bypass graft, and all-cause mortality in 6 weeks. Results: The data of 154 patients was analyzed. Of these, 121 patients had a negative CARE score of ≤1 and 33 individuals had a positive CARE score. Of those with a negative CARE score, only 1 (3%) experienced an adverse cardiac event while in those with a positive CARE score, 26 individuals (16.88 %) experienced MACE. The sensitivity of the CARE rule was 96.15% and the specificity was 25% with a negative likelihood ratio (LR-) of 0.15. The indices for HEART score were 88%, 59.69%, and 0.2, respectively. In comparison, physicians' gestalt had a sensitivity of 96%, specificity of 49.22%, and a LR- of 0.08. Of note, utilizing the CARE rule with a cut-off of |