Background¦ Omega-3 fatty acids showed the effect of decreasing triglyceride level, stabilizing atheromatous plaque and improving survival in patients with coronary artery diseases. Omega-3 fatty acids have been considered beneficial for autonomic cardiovascular function. This study was designed to evaluate the effects of omega-3 fatty acids on lipoproteins and heart rate variability in patients with mixed dyslipidemia. Methods¦ This study was a prospective, randomized, open label study. Patients who had mixed dyslipidemia with high triglyceride level (200-499 mg/dL) and total cholesterol level over 200 mg/dL were enrolled. After run-in period of 6 weeks, patients were randomized to two groups and received combination treatment with omega-3 fatty acids 4g and simvastatin 20 mg daily or monotherapy with simvastatin 20 mg for 6 weeks. The primary objective was to compare the change of triglyceride level from baseline to week 6 between two groups. The secondary objectives were the changes of other lipoprotein profiles including apolipoprotein(apo) B/A1 ratio and high sensitivity C-reactive protein (hsCRP) and the change of parameters of heart rate variability. Results¦ 171 patients were screened and 62 patients (mean 58 years of age, male 41%, BMI 25.6 kg/m2) were randomized to two treatment groups. After 6 weeks' treatment, triglyceride level decreased 41.0% in combination treatment and 13.9% in simvastatin monotherapy group (from 309.2 mg/dL to 177.7 mg/dL in combination treatment, from 294.6 mg/dL to 238.3 mg/dL, p=0.0007). No significant differences were seen in the changes of low density lipoprotein cholesterol, high densitylipoprotein cholesterol, total cholesterol, apoB/A1 ratio and hsCRP levels between two groups. Neither combination therapy nor simvastatin monotherapy induced significant changes in the parameters of heart rate variability. Tolerability profiles were not significantly different between two groups. Conclusion¦ Combination therapy of omega-3 fatty acids and simvastatin decreased triglyceride level more significantly than simvastatin alone. The effect of omega-3 fatty acids on heart rate variability was not demonstrated in this study.