Myocardial fractional flow reserve (FFR) has emerging clinical utility and prognostic value in medically stabilized patients with non-ST-segment elevation myocardial infarction (NSTEMI). The aim of this study was to investigate whether measurement of FFR compared to coronary angiography alone improves diagnostic efficiency in patients with NSTEMIs. One hundred consecutive patients with NSTEMIs who had previously undergone clinically indicated FFR measurements were included. In a simulated decision exercise, 5 interventional cardiologists retrospectively and independently reviewed the clinical history and coronary angiogram of each patient and then made a treatment decision. FFR results were then disclosed, and the same cardiologists were asked to review their initial treatment decisions. A p value <0.05 indicates a difference between cardiologists. The proportion of patients allocated to each treatment option initially differed among the 5 cardiologists (p = 0.0061). Forty-two percent of all FFR measurements were made in culprit lesions. After FFR disclosure, the number of patients in whom the treatment decisions made by each cardiologist independently conformed (and so represented the majority with ≥3 of the 5 cardiologists) increased from 65% to 91% (p = 0.0094). After FFR disclosure, the cardiologists changed their initial treatment plans in 46% of patients (p = 0.0016). Changes in favor of medical therapy occurred in 24% of patients (p = 0.0016), and this increase was associated with reductions in "deferred" management (p = 0.0067), single-vessel percutaneous coronary intervention (p = 0.0052), and multivessel percutaneous coronary intervention (p = 0.046). In conclusion, FFR measurement reduced diagnostic variability and changed cardiologists' treatment decisions for patients with NSTEMIs.