Background Although the development of a coronary guidewire mounted with a pressure sensor has facilitated the measurement of pressure-derived fractional flow reserve (FFR) to assess the functional severity of coronary artery stenoses, the theoretical limitations include diabetes mellitus because of the associated microvascular abnormalities. Methods and Results In the present study 304 vessels and their coronary territories in 96 diabetic and 149 nondiabetic patients were evaluated by pressure-derived FFR and thallium-201 single photon emission computed tomography (SPECT) to determine the applicability of measuring FFR in diabetic subjects. The best cut-off value for FFR to detect myocardial ischemia, as demonstrated by ²⁰¹Tl SPECT, was 0.725 in the diabetic and 0.745 in the nondiabetic patients. Sensitivity and specificity were similar for the 2 groups (83% and 75% (diabetic) vs 79% and 83%). However, diabetic patients with homoglobin (Hb) A_1c ≥7.0% showed lower specificity in comparison with those having HbA_1c <7.0% (64 vs 88%; p=0.045); however, sensitivities were similar (83 vs 83%; p=NS). Conclusions The cut-off value of 0.75 for FFR can detect myocardial ischemia in diabetic patients, although the adequacy of glycemic control should be taken into consideration when assessing the FFR measurements. (Circ J 2004; 68: 993 - 998)