Background Interstitial collagen, especially type 1, is a major component of atherosclerotic plaques and the matrix metalloproteinases (MMP) 1, 8 and 13 can initiate collagen breakdown. MMP-8 degrades type I collagen preferentially and more potently than MMP-1 or MMP-13. Although MMP-8 was thought to be produced only by neutrophils, it was recently reported to also be produced by endothelial cells, smooth muscle cells and macrophages in plaques. Methods and Results Plasma MMP-8 concentrations were measured in 250 patients undergoing coronary angiography for coronary artery disease (CAD: > 50% stenosis), which was found in 181 patients, of whom 69 had 1-vessel, 66 had 2-vessel, and 46 had 3-vessel disease. Compared with 69 patients without CAD, the 181 with CAD had higher MMP-8 concentrations (3.5 vs 3.0 ng/ml, p < 0.001). There was a stepwise increase in MMP-8 concentration depending on the number of stenotic vessels: 3.2 in 1-vessel, 3.6 in 2-vessel, and 4.3ng/ml in 3-vessel disease (p < 0.001). Multivariate analysis showed that MMP-8 concentration was independently associated with CAD. The odds ratio for CAD was 1.22 (95% confidence interval = 1.07-1.39) for a 1 ng/ml increase in MMP-8 concentration. Conclusions Plasma MMP-8 concentration is associated with the presence and severity of CAD.