Background: Circulating monocytes can be divided into 2 subsets typically identified by the expression of CD14 and CD16. Although previous studies have shown that circulating monocytes contribute to the progression of coronary atherosclerotic lesions, the relationship between the severity of coronary artery disease (CAD) and the 2 distinct monocyte subsets has not previously been evaluated. We investigated the relationship between the monocyte subsets and the severity of CAD assessed by coronary angiography (CAG) in patients with stable angina pectoris (SAP). Methods and Results: We enrolled 125 patients who underwent diagnostic CAG. Patients were divided into 3 groups: those without CAD, those with single-vessel disease (SVD), and those with multiple-vessel disease (MVD). In addition, the severity of CAD was evaluated by Gensini score. The 2 monocyte subsets (CD14⁺CD16^– and CD14⁺CD16⁺) were measured by flow cytometry. Circulating CD14⁺CD16⁺ monocytes were more frequently observed in patients with MVD than in those with SVD or without CAD. The proportion of CD14⁺CD16⁺ monocytes positively correlated with Gensini score (r=0.618, P<0.001). Multivariate logistic regression analysis revealed that the proportion of CD14⁺CD16⁺ monocytes was an independent contributor to MVD (odds ratio: 1.475; 95% confidence interval: 1.273–1.708, P<0.001). Conclusions: A preferential increase in peripheral CD14⁺CD16⁺ monocytes may be closely related to the severity of CAD in patients with SAP.  (Circ J 2012; 76: 2412–2418)