Background: The metabolic syndrome is a cluster of clinical characteristics thought to be associated with increased coronary risk. This analysis evaluates angiographic progression of coronary disease in women who are postmenopausal with and without the metabolic syndrome enrolled in the Women's Angiographic Vitamin & Estrogen (WAVE) trial, a randomized, controlled trial of hormone therapy and antioxidant vitamins. Methods: A total of 425 women who are postmenopausal and have angiographic coronary disease were enrolled at 7 clinics between July 1997 and August 1999. Women were categorized as having the metabolic syndrome when they met the National Cholesterol Education Program Adult Treatment Panel III definition. Coronary angiograms were performed at baseline and after 2.8 ± 0.9 years (mean ± SD). Quantitative coronary angiographic analysis was performed at a core laboratory. Results: Women with the metabolic syndrome (177/294, 60%) were more likely to be taking cholesterol-lowering medication (65% vs 51%, P = .01) and had higher body mass index (33 ± 6 vs 28 ± 6 kg/m2, P < .001). The mean reduction in minimum lumen diameter was greater (-0.041 ± 0.151 vs -0.023 ± 0.148 mm/year, P = .33) and new lesions were more frequent (34% vs 23%, P = .054) in women with the metabolic syndrome. In multivariate analysis, the metabolic syndrome was not an independent predictor of angiographic disease progression. However, clinical events (myocardial infarction, stroke, or coronary death) were more frequent among women with the metabolic syndrome (P = .02). Conclusion: The metabolic syndrome was prevalent among postmenopausal women with coronary disease enrolled in the WAVE trial. Having the metabolic syndrome was not independently associated with changes in minimum lumen diameter or the development of new or progressing coronary lesions, but did confer an increased risk of clinical cardiovascular events.