Objective: Apolipoprotein A5 (apoA5) exhibits triglyceride (TG) lowering effects in mouse models and has been associated with coronary artery disease (CAD) risk factors in humans. Although the underlying mechanism for the TG-lowering effect of apoA5 is still obscure, several evidences indicate that apoA5 stimulates lipoprotein lipase (LPL) activity. Thus, we investigated the apoA5/TG relationship and the association of plasma concentrations of apoA5 with the risk of CAD in a case-control study design. Methods: ApoA5, TG, insulin, free fatty acid (FFA) and lipoprotein profiles were determined cross-sectionally in 777 healthy control males and 367 male patients with angiographically confirmed CAD. Results: Plasma apoA5 concentration was lower in CAD patients than controls (193짹5 vs. 237짹4 ng/ml, P<0.001). In addition, values in the second and top tertiles of apoA5 were associated with a decreased odds ratio (OR) for CAD when compared with values in the bottom tertile; OR for apoA5 top tertile was 0.33 (95% CI, 0.23-0.47) in the age- and BMI-adjusted model and 0.35 (95% CI, 0.23-0.56) after additional adjustment for smoking and drinking status, blood pressure, TG and HDL-cholesterol. After adjustment for age and BMI, in normotriglyceridemic controls (TG<150 mg/dL, n=509), apoA5 was negatively correlated with serum TG (r=-0.188, P<0.001) and insulin (r=-0.185, P<0.001). However, apoA5 was positively correlated with serum TG in hypertriglyceridemic controls (TG���150 mg/dL, n=268) (r=0.246, P<0.001) and CAD patients (r=0.177, P<0.01). Regardless to fasting TG levels and CAD, apoA5 concentration was positively correlated with HDL-cholesterol and fasting FFA levels. Conclusion: This result shows the association of elevated concentration of apoA5 with reduced CAD risk. This could be compatible with negative correlations of apoA5 with TG and insulin, although these correlations were affected by fasting TG levels.