Strong evidence suggests that C-reactive protein (CRP) is a novel risk factor for cardiovascular disease. We aimed to examine the effect of soy isoflavones on circulating CRP concentrations in postmenopausal women by conducting a meta-analysis of randomized controlled trials. We performed a literature search using PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases in December 2010 for randomized controlled trials conducted in postmenopausal women, using soy foods with isoflavones or isoflavone extracts as treatment, and with a report of CRP change. A meta-analysis was performed using a fixed-effects model or a random-effects model to calculate the combined effect size. In addition, subgroup and metaregression analyses were carried out to examine the influences of study designs and participant characteristics on the effect estimates. A pooled analysis of 14 trials showed a slight, but not significant, reduction of 0.17 mg/L (95% CI, -0.38 to 0.04; P = 0.12) in CRP concentrations among postmenopausal women with soy isoflavone intervention compared with controls. No substantial heterogeneity was observed. Subgroup analyses showed that soy isoflavones significantly lowered CRP by 0.70 mg/L (95% CI, -1.17 to -0.23; P = 0.003) among women with baseline CRP concentrations greater than 2.2 mg/L. No significant changes in CRP were observed in the other subgroups. Metaregression analysis further revealed that baseline CRP was a potential effect modifier of isoflavone treatment in lowering CRP. The present meta-analysis found insufficient evidence that soy isoflavones significantly reduce CRP concentrations in postmenopausal women. However, soy isoflavones may produce a significant reduction in CRP among postmenopausal women with elevated CRP.