Background: Studies have demonstrated that patients with diets high in w-3 fatty acids have a lower risk of adverse cardiovascular events. C-reactive protein (CRP), a marker of inflammation, is a strong predictor of future cardiovascular events. w-3 fatty acids have been shown to have anti-inflammatory properties. However, there is a paucity of data examining the effect of =-3 fatty acids on CRP levels. This randomized, double-blind, placebocontrolled trial tested the hypothesis that treatment with w-3 polyunsaturated fatty acids (n-3 PUFAs) would reduce serum high-sensitivity CRP levels. Materials & methods: Fifty three patients with elevated baseline CRP (?3 mg/l) were randomized to n-3 PUFA (27 patients) or placebo (26 patients). Patients with active infection, inflammatory disease, baseline CRP ?10 mg/l or those started on HMG-CoA reductase inhibitor therapy during the study period were excluded. The primary end point was CRP level following 8 weeks of treatment. Results: After 8 weeks of treatment with the study drug, the median CRP level in the n-3 PUFA group was 3.4 mg/l compared with 4.0 mg/l in the placebo group (p = 0.36). After controlling for baseline CRP, there was a significant percentage decrease in CRP from baseline in the n-3 PUFA group (-40.3%; p = 0.009) but not in the placebo group (-16.4%; p = 0.32) Conclusion: Treatment for 8 weeks with w-3 fatty acids resulted in a significant percentage reduction of CRP levels as compared with baseline, a finding not seen with placebo.