OBJECTIVES: We aimed to validate the technique of measuring the coronary flow reserve (CFR) with coronary pressure measurements against an established thermodilution technique. BACKGROUND: The CFR has traditionally required measurement of coronary blood flow velocity with the Doppler wire and, more recently, using a thermodilution technique with the coronary pressure wire. However, recent work has suggested that the CFR may be derived from pressure measurements alone (the ratio of the square root of the pressure drop across an epicardial stenosis during hyperemia to that value at rest). This depends on the assumption that friction losses across a coronary stenosis are negligible. METHODS: We compared pressure-derived CFR values with those obtained by the thermodilution technique using the intracoronary pressure wire in 38 stenoses in 34 patients with significant coronary stenoses undergoing percutaneous intervention. We also compared these two techniques of measuring CFR in 25 stenoses (6 vessels) artificially created by inflating small balloons within a stented coronary artery after percutaneous intervention. RESULTS: There is a close linear relationship between pressure-derived and thermodilution CFR in native (r(2) = 0.52; p < 0.001) and artificial stenoses (r(2) = 0.54; p < 0.05), although the pressure-derived technique appears to systematically underestimate CFR values in both situations. This applies to native and artificial stenoses. CONCLUSIONS: Coronary flow reserve cannot be measured merely with pressure alone, and it cannot be safely assumed that friction losses are negligible across a native coronary stenosis. These data suggest that friction loss is an important determinant of the pressure gradient along an atherosclerotic coronary artery.