High-sensitivity C-reactive protein is associated with increased risk of cardiovascular events. Consequently, the predictive value of this protein in patients with symptomatic peripheral arterial disease was examined. In all, 452 patients with symptomatic peripheral arterial disease had high-sensitivity C-reactive protein measured at baseline (mean follow-up = 2.1 +/- 1.4 years). Events were defined as primary (death, amputation, or peripheral revascularization) or secondary (lower limb thrombosis, myocardial infarction, or stroke).The level of high-sensitivity C-reactive protein was significantly higher among those dying (P = .04), those who needed amputation (P = .01), and those developing an overall secondary endpoint (P = .02). By receiver-operating characteristic curve analysis, the optimal cutoff point was constantly approximately 10 to 20 mg/L with a sensitivity and specificity of 56% to 63% and 54% to 56%, respectively. Baseline levels of high-sensitivity C-reactive protein are associated with future arterial events in symptomatic peripheral arterial disease patients but cannot stand alone as a predictive tool.