Backround: Altered coronary reactivity frequently occurs in women with chest discomfort both with and without obstructive coronary artery disease (CAD). Among those with obstructive CAD, the endothelial-dependent and non-endothelial dependent components of this altered reactivity have been associated with adverse outcomes. The clinical events among those with altered coronary reactivity but without obstructive CAD are not well defined. Methods: We evaluated 169 women with suspected myocardial ischemia who had no obstructive CAD at coronary angiography. Coronary reactivity was assessed by measuring flow reserve (CFR) with adenosine (endothelial-dependent) and change in vessel diameter (DIAM) following acetylcholine (non-endothelial dependent). Women were then followed for major adverse events (death, myocardial infarction, stroke, or hospitalization for heart failure) as well as hospitalization for recurrent angina by annual telephone contact over a median of 6.0 years. Results: Mean age was 54 ± 10 years, 15% were non-white, 37% had abnormal CFR (<2.32), and 47% had abnormal DIAM (no change or constriction). Of the women receiving both coronary reactivity tests, results were concordant in only 52%. Major events occurred in 16% (28/169) of which 5% (8/169) died. An additional 24% (41/169) were hospitalized for worsening angina. Major adverse events were predicted by abnormal CFR (27% vs 10%, p = 0.006) but not abnormal DIAM, while abnormal DIAM, but not CFR, predicted hospitalization for angina. Conclusion: Endothelial-dependent and non-dependent coronary dysfunction coexist in approximately one-half of women tested without angiographic evidence of CAD and appear to predict different types of adverse outcomes during follow-up. These results should foster developement of new diagnostic and treatment strategies targeting both endothelial and non-endothelial (e.g. vascular smooth muscle) dependent coronary dysfunction in women.