The study aims to develop a decision pathway based on HEAR score and 0 h high-sensitivity cardiac troponin T (hs-cTnT) to safely avoid a second troponin test for suspected non-ST elevation myocardial infarction (NSTEMI) in emergency departments. A HEAR score consists of history, electrocardiogram, age, and risk factors. A HEAR pathway is established using a Bayesian approach based on a predefined safety threshold of NSTEMI prevalence in the rule-out group. In total, 7131 patients were retrospectively enrolled, 582 (8.2%) with index visit NSTEMI and 940 (13.2%) with 180-day major adverse cardiovascular events (MACE). For patients with a low-risk HEAR score (0 to 2) and low 0 h hs-cTnT (<14 ng/L), the HEAR pathway recommends early discharge without further testing. After the HEAR pathway had been applied to rule out NSTEMI, the negative predictive value of index visit NSTEMI was 100.0% (95% CI, 99.8% to 100.0%) and false-negative rate of 180-day MACE was 0.40% (95% CI, 0.18% to 0.87%). Compared with the 0 h hs-cTnT < limit of detection (LoD) strategy (<5 ng/L), the HEAR pathway could correctly reclassify 1298 patients without MACE as low risk and lead to a 18.2% decrease (95% CI, 17.4–19.1%) in the need for a second troponin test. The HEAR pathway may lead to a substantial and safe reduction in repeated troponin test for emergency department patients with suspected NSTEMI.