BACKGROUND Although increased coronary microvascular resistance (CMR), resulting in coronary microvascular dysfunction, is speculated to be responsible for myocardial ischemia in patients with cardiac syndrome X (CSX), it has never been directly demonstrated, and the correlation between CMR and severity of myocardial ischemia has not been elucidated in this setting. This study aimed to ascertain the increased CMR directly and to explore the relationship between CMR and severity of ischemia in patients with CSX. RESULTS We studied 18 patients with CSX and 18 age- and sex-matched control subjects. Thermodilution-derived coronary flow reserve and index of microvascular resistance were measured using a pressure-temperature sensor-tipped coronary wire. Exercise treadmill test was performed by the Bruce protocol for calculating Duke treadmill score. Coronary flow reserve was significantly lower (2.37±0.81 versus 3.68±0.72; P<0.001) and index of microvascular resistance was higher (33.1±7.9 versus 18.8±5.6 U; P<0.001) in patients with CSX compared with those in control subjects. The Duke treadmill score was correlated positively to coronary flow reserve (r=0.539; P=0.021) and negatively to index of microvascular resistance (r=-0.742; P<0.001) in patients with CSX. CONCLUSIONS Using an intracoronary thermodilution method, we for the first time directly demonstrated an increased microvascular resistance in patients with CSX. Furthermore, severity of ischemia was found to be intimately associated with CMR in this setting.