Objectives. The purpose of this study was to examine the relation among the angiographic severity of coronary artery lesions, coronary flow velocity and translesional pressure gradients. Background. Determination of the clinical and hemodynamic significance of coronary artery stenosis is often difficult and inexact. Angiography has been shown to be an imperfect tool for determining the physiologic significance of eccentric or irregular coronary lumen narrowing. Methods. Using a 0.018-in. (0.046 cm) intracoronary Dopplertipped angioplasty guide wire, spectral flow velocity data both proximal and distal to coronary stenoses were compared with translesional pressure gradient measurements and angiographic data obtained during cardiac catheterization in 101 patients. There were 17 patients with normal angiographic findings and 84 with coronary artery disease, with lesions ranging from 28% to 99% diameter narrowing. Patients with coronary disease were assigned to two groups on the basis of translesional gradients at rest. Group A (n = 56) had gradients <20 mm Hg, and Group B (n = 28) had gradients ≥20 mm Hg. Results. Proximal average peak velocity, diastolic velocity integral and total velocity integral were slightly but statistically lower in Group A; however, the distal average peak velocity and diastolic and total velocity integrals were all markedly (all p < 0.01) decreased in patients with gradients ≥20 mm Hg (Group B). In addition, the ratio of proximal to distal total flow velocity integral was higher in Group B (2.4 ± 1.0) than in group A (1.1 ± 03, p < 0.001). There was a strong correlation between translesional pressure gradients and the ratios of the proximal to distal total flow velocity integrals (r = 0.8, p < 0.001), with a weaker relation between quantitative angiography and pressure gradients (r = 0.6, p < 0.001). In angiographically intermediate stenoses (range 50% to 70%), angiography was a poor predictor of translesional gradients (r = 0.2, p = NS), whereas the flow velocity ratios continued to have a strong correlation (r = 0.8, p < 0.001). Only two patients with a proximal/distal total flow velocity ratio <1.7 had a translesional gradient >30 mm Hg. Both patients had a very proximal lesion in a nonbranching right coronary artery. Conclusions. These data demonstrate that in branching human coronary arteries, a close relation exists between translesional hemodynamics and distal coronary flow velocity. Translesional coronary flow velocity is a new and easily applicable method for determining the hemodynamic significance of coronary artery stenoses that is superior to angiography and can be applied at the time of diagnostic catheterization. These data will provide a rational approach to making decisions on the use of coronary interventional techniques when angiographic findings are questionable.