Ambient cold exposure may induce myocardial ischemia by precipitating coronary artery constriction and a decrease in coronary blood flow. Estrogen has vasoactive properties that may prevent abnormal coronary constriction in a sex-independent manner. The purpose of this study is to determine whether estrogen acutely abolishes abnormal coronary responses to cold exposure in men. Randomized, double-blinded placebo-controlled clinical trial. Cardiac catheterization laboratory. Men referred for routine diagnostic coronary angiography who exhibit abnormal coronary artery constriction in response to a 90-s cold pressor test (CPT). Intravenous conjugated estrogens (1.25 mg) vs. placebo. Rate-pressure product, coronary cross-sectional area (CSA), and coronary blood flow responses to the CPT were measured before and 15 min after intervention. In 12 men with CPT-induced coronary constriction who were assigned to estrogen, CPT induced a mean 21.8% decrease in coronary CSA (p < 0.01) and a nonsignificant change in coronary flow. After estrogen, the repeated CPT induced a 16.3% increase in CSA (p < 0.01) and a 54.9% increase in flow (p < 0.01). CSA and coronary flow responses to CPT were significantly different before and after estrogen (p < 0.01). In contrast, placebo was not associated with changes in CSA or coronary flow responses to CPT in eight men. In men, conjugated estrogens acutely abolish abnormal coronary constriction and improve coronary blood flow responses to an exogenous cold stimulus. These results suggest that estrogen favorably alters coronary vasoreactivity in men.