There are limited data regarding the utility of troponin testing in patients presenting with non-cardiovascular (CV) symptoms as the primary manifestation. The study population comprised 2057 patients who presented to the emergency department (ED) of a US healthcare system with non-CV symptoms as the primary manifestation between January and September 2018. We compared the effect of high-sensitivity cardiac troponin T (hs-cTnT) (n = 901) after its introduction vs. 4th generation cTnT (n = 1156) on the following outcomes measures: ED length of stay (LOS), coronary tests/procedures (angiography or stress test), and long-term mortality. Mean age was 64 ± 17 yrs., and 47% were female. Primary non-CV manifestations included pneumonia, obstructive pulmonary disease, infection, abdominal-complaint, and renal failure. Mean follow up was 9 ± 4 months. Patients' demographics and medical history were clinically similar between the two troponin groups. A second cTn test was obtained more frequently in the hs-cTnT than cTnT (84% vs. 32%; p < 0.001), possibly leading to a longer ED stay (8.1 ± 8.2 h vs 5.6 ± 3.4 h, respectively; p < 0.001). Coronary tests/procedures were performed at a significantly higher rate in the hs-cTnT than cTnT following the introduction of the hs-cTnT test (28% vs. 22%, p < 0.001). Multivariate analysis showed that following the introduction of hs-cTnT testing, there was a significant 27% lower risk of long-term mortality from ED admission through follow-up (HR = 0.73, 95%CI 0.54–0.98; p = 0.035). In conclusion, we show that in patients presenting primarily with non-CV disorders, the implementation of the hs-cTnT was associated with a higher rate of diagnostic coronary procedures/interventions, possibly leading to improved long-term survival rates.