Objective: To evaluate past oral contraceptive use and angiographic coronary artery disease in women. Setting: Academic medical centers. Patient(s): Six hundred seventy-two postmenopausal women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) with coronary risk factors undergoing coronary angiography for suspected myocardial ischemia. Intervention(s): Past oral contraceptive use, assessed by reproductive questionnaire. Main Outcome Measure(s): Quantitative coronary artery disease, assessed by a core angiography laboratory. Result(s): Past oral contraceptive use was associated with a lower mean coronary artery disease severity index score (mean ± SD: 11.8 ± 10.3 vs. 18.7 ± 17.3) compared with non-prior users, despite age adjustment. Past oral contraceptive use remained a significant independent negative predictor of coronary artery disease severity when adjusting for coronary risk factors, including age, diabetes mellitus, triglycerides, low-density lipoprotein cholesterol, smoking, aspirin use, and lipid-lowering medication (model R2 = 0.19). The modeling indicated that past oral contraceptive use was associated with a 2.44 lower coronary artery disease severity score index. There was no apparent relationship between duration of past oral contraceptive use and the coronary artery disease severity index score. Conclusion(s): Past oral contraceptive use is associated with less coronary artery disease, measured by quantitative coronary angiography, among postmenopausal women with suspected myocardial ischemia. These findings suggest that a prospective study should address the hypothesis that past oral contraceptive use during the premenopausal years might offer women protection from atherosclerotic coronary disease later in life. © 2006 American Society for Reproductive Medicine.