This study investigated the relation among serum C-reactive protein (CRP), number of complex coronary lesions, and adverse cardiovascular events at 1 year. Univariate and multivariate analyses were performed. Of 283 patients who had acute coronary syndrome, a single complex lesion was present in 32%, multiple complex lesions were identified in 23%, and no complex lesion was documented in 45%. On multivariate analysis, CRP was independently associated with the presence of multiple complex coronary lesions (p <0.0001); there was a striking association between increments in CRP titers and number of complex lesions (CRP levels of 0.22 mg/dl in patients who had 0 lesion, 0.53 mg/dl in patients who had 1 lesion, and 1.85 mg/dl in patients who had multiple complex lesions, p <0.0001), and high serum CRP levels independently predicted adverse outcome (p = 0.03). In conclusion, the presence of multiple complex plaques was the most powerful predictor of adverse outcome (hazard ratio 2.88, p = 0.0007), predominantly in those who had high CRP levels (p = 0.004).