Background: Because the mechanisms of the biological effects of fenofibrate and statins therapies differ, we studied the vascular responses and tolerability to fenofibrate(Feno) and atorvastatin(Ator) therapies in patients with mixed hyperlipidemia. Methods: We administered micronized Feno 200 mg or Ator 10 mg daily during 2 months with washout 2 months to 42 patients. This study was randomized, double-blind, two treatment period, crossover in design. Results: Feno or Ator therapies significantly improved the percent flow-mediated dilator response (FMD) to hyperemia and reduced C-reactive protein (CRP) levels and fibrinogen levels, compared with baseline measurements. There were significant correlations between the percent changes in HDL-C levels and the percent changes in FMD (r=0.308 and p=0.047) and between the percent changes in LDL-C levels and the percent changes in FMD (r= 0.403 and p=0.009) after Feno therapy. Of interest, Ator therapy significantly reduced TC (p<0.001), LDL-C (p<0.001), and Apo B (p=0.023), compared with Feno and Feno therapy significantly changed TG (p<0.001), HDL-C (p=0.004), Apo A-I (p=0.036), and fibrinogen (p=0.006), compared with Ator. No patient discontinued a therapy due to side effects. Conclusions: Feno and Ator are safe and showed different anti-atherogenic effects, suggesting the possible synergistic effect of combination therapy.