We evaluated the effect of reduced activities of protein C (PC) and protein S (PS) on the progression of peripheral arterial disease (PAD). We measured PC and PS activities in 106 patients with PAD and 44 patients with abdominal aortic aneurysm (AAA) in the same period. The incidences of PC deficiency in PAD and AAA were 4.7% and 4.5%, respectively, and those of PS were 14.1% and 11.4%, respectively; these incidences were much higher than those in the normal population. The PC and PS activities were significantly lower in patients having critical limb ischemia (CLI) than in patients with intermittent claudication. In particular, lower PC activity and female gender were determinant factors of CLI in multivariate logistic regression analysis. We suggest that PC deficiency is an independent predictor for the progression of CLI.