We prospectively investigated the relation of high-sensitivity C-reactive protein (hs-CRP) to coronary vasospasm and no hemodynamically significant coronary artery disease (CAD) in a sample of 428 patients who underwent coronary angiography. These patients were assigned to 1 of 3 groups. The control group consisted of 66 patients who had no coronary vasospasm and no hemodynamically significant CAD. The vasospasm group consisted of 116 patients who had coronary vasospasm and no hemodynamically significant CAD. The acute coronary syndrome (ACS) group consisted of 246 patients who had ACS and hemodynamically significant CAD. Serum hs-CRP was measured immediately before coronary angiography. Patients were followed for subsequent cardiac events and mortality. Median hs-CRP levels in the control, vasospasm, and ACS groups were 1.0, 5.5, and 8.2 mg/L, respectively. The proportion of hs-CRP increased from the lowest to the highest tertile in the control, vasospasm, and ACS groups, respectively. In the control and vasospasm groups, multivariate analysis showed that hs-CRP was independently associated with a diagnosis of coronary vasospastic angina pectoris (odds ratio 68.74, 95% confidence interval 8.03 to 588.71, p<0.001). During a median follow-up period of 26 months (range 0.4 to 48), 27 cardiac deaths occurred in the ACS group, whereas no cardiac death occurred in the control and vasospasm groups. In conclusion, serum hs-CRP level measured immediately before coronary angiography was an independent marker of coronary vasospasm in patients who had no hemodynamically significant CAD.