BACKGROUND Endomyocardial biopsy (EMB) remains the gold standard for detecting acute rejection (AR) after heart transplantation (HTx). Non-invasive detection of AR thus far remains a challenge. Several studies have demonstrated that highly sensitive cardiac troponin T (hs-cTnT) concentrations have a low positive predictive value for diagnosing AR. Nevertheless, hs-cTnT proved to be useful for ruling out AR after HTx. An hs-cTnT concentration <17 ng/L, a value close to that used for rule-in or rule-out myocardial infarction, was associated with a 100% negative predictive value of AR. However, the cost-effectiveness of a strategy with the use of hs-cTnT for ruling out AR in HTx patients remains to be proven. METHODS The cost-effectiveness of hs-cTnT determination for ruling out AR was assessed, comparing the costs of hs-cTnT measurements in 305 blood samples obtained at the time of EMB. Eighteen samples were excluded because the EMB was not assessable. RESULTS Hs-cTnT determination cost 16.00€ per sample, whereas EMB cost 1752.00€ per biopsy; cost estimations included direct and indirect (30%) charges. Thirty-nine (13.6%) of the 287 blood samples presented hs-cTnT concentrations <17 ng/L; in none of them was an AR >2R degree found in the EMB. The cost of the assessment in the 287 blood samples and biopsies was of 4592.00€ for hs-cTnT and 502,824.00€ for EMB. Hs-cTnT systematic measurement would have avoided 39 EMB, with a saving of 68,328.00€, which represents the 13.5% of the total budget expended in these cases. CONCLUSIONS The use of hs-cTnT values to rule out the need of EMB for AR diagnosis after HTx appears to be a cost-effective procedure.