Women younger than 75 years with stable angina or acute coronary syndrome have higher cardiac mortality than similarly aged men, despite less obstructive coronary artery disease. To determine whether the myocardial structure and coronary microvasculature of women differs from that of men, we performed histological analysis of biopsies from nonischemic left ventricular myocardium from 46 men and 11 women undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation, or furosemide therapy. The 2 patient groups had similar clinical characteristics, apart from a lower body surface area (BSA) in women (P = 0.0015). Women had less interstitial fibrosis than men (P = 0.019) but similar perivascular fibrosis. Arteriolar wall area/circumference ratio, a measure of arteriolar wall thickness, was 47% greater in women than men (P = 0.012). Cardiomyocyte width and diffusion radius were positively correlated, and capillary length density was negatively correlated with BSA (P < 0.05). Whereas cardiomyocyte width, capillary length density, diffusion radius, and cardiomyocyte width/BSA ratio were similar for men and women, women had a greater diffusion radius/BSA ratio (P = 0.0038) and a greater diffusion radius/cardiomyocyte width ratio (P = 0.027). Women also had lower vascular endothelial growth factor (VEGF) receptor-1 levels (P = 0.048) and VEGF receptor-1/VEGF-A ratio (P = 0.024) in plasma. We conclude that women with extensive coronary artery disease have greater arteriolar wall thickness and diffusion radius relative to BSA and to cardiomyocyte width than men, which may predispose to myocardial ischemia. Additional studies of larger numbers of women with less extensive coronary artery disease are required to confirm these findings.