Aims: Soy phytoestrogens are popular, but information on their coronary effects in patients with suspected ischemic heart disease is limited. Accordingly, we investigated the relationship between blood phytoestrogen levels and coronary reactivity in women with suspected myocardial ischemia referred for coronary angiography. Methods: Coronary flow velocity reserve (CFVR) and volumetric flow reserve (VFR) to adenosine (ADO) and nitroglycerin (NTG) (nonendothelial-dependent responses) and acetylcholine (ACH) (endothelial-dependent response) were assessed in 106 women from the Women's Ischemia Syndrome Evaluation (WISE). Blood phytoestrogen (daidzein and genistein) and estrogen (estradiol) levels were correlated with coronary reactivity measures. Results: Participants were mostly postmenopausal (79%), mean age 56 years, and 24% had obstructive coronary artery disease (CAD) at angiography. Genistein blood levels were negatively correlated with nonendothelial-dependent coronary flow responses. The highest genistein fertile (>6.1 ng/mL) had a CFVR of 2.1 ± 0.5 (mean ± SD) and VFR ADO of 1.0 ± 0.6, and both were significantly (p = 0.0001) lower compared with the other genistein tertiles combined. Similar associations were noted for CFVRNTG and VFRNTG (p = 0.03 and p = 0.01, respectively). The highest genistein fertile was associated with lower CFVR ACH compared with the other tertiles (p = 0.03). In multivariable modeling, blood genistein levels were significant independent predictors of coronary flow responses to ADO. There were no significant correlations between coronary reactivity variables and daidzein or endogenous estrogen. Conclusions: In women with suspected myocardial ischemia, higher genistein blood levels are associated with impaired nonendothelial-dependent and endothelial-dependent coronary microvascular function. © Mary Ann Liebert, Inc.