Objective: The effects of fenofibrate on C-reactive protein (CRP) levels are controversial. We investigated the effect of fenofibrate on C-reactive protein (CRP) and variables determining changes. Methods: This case-control study enrolled 280 hypertriglyceridemic patients who were managed either with 200 mg of fenofibrate (Fenofibrate group, n=140) or with general measures (Control group, n=140). CRP levels were measured before and after 2 months of therapy. Results: CRP decreased in both fenofibrate (p=0.003) and control (p=0.048) groups. Changes in CRP were not different between the two groups (-0.24짹1.56 versus -0.14짹1.69 mg/dL, p=0.27) and were associated with baseline CRP levels (r=-0.47, p=0.000). In patients with baseline CRP ��� 1 mg/dL, CRP also decreased in both groups (p=0.000 and p=0.001 respectively), however, more in the fenofibrate group than in the control group (-0.79짹1.90 versus -0.66짹1.77 mg/L, p=0.025). The reduction of CRP was associated with higher baseline CRP (r=-0.29, p=0.001, figure), lower body mass index (r=0.23, p=0.007), and fenofibrate therapy (r=0.19, p=0.025). CRP decreased more in the fenofibrate group than in the control group in patients with body mass index ��� 26 kg/m2 with borderline significance (-1.21짹1.82 versus -0.89짹1.92 mg/dL, p=0.097). In patients with high density lipoprotein-cholesterol < 40 mg/dL, only fenofibrate group reduced CRP (p=0.006). Conclusions: Fenofibrate reduced CRP in non-obese hypertriglyceridemic patients with high CRP and/or low high density lipoprotein-cholesterol. This finding suggests that fenofibrate may have anti-inflammatory effect in selected patients with high risks for cardiovascular diseases.